The effect of tryptophan plus methionine, 5-azacytidine, and methotrexate on adjuvant arthritis of rat.

Within the wider framework of our studies on the genesis of rheumatoid arthritis we have investigated the two signal processes in arthritis: adenoribosylation of proteins and DNA methylation. Arthritis can be induced when Freund's complete adjuvant is applied to rats. This form of arthritis can then be reduced or even totally suppressed through the application of several different substances. In the present article we have investigated if the effect of two of these substances, 5-azacytidine and methotrexate can be influenced by the application of tryptophan plus methionine. When applied singly, these latter two substances are known to reduce the formation of arthritis. This effect is intensified by a combination of tryptophan plus methionine. Application of tryptophan plus methionine without methotrexate or 5-azacytidine causes an enhanced development of an adjuvant induced arthritis.

Spontaneous bacterial arthritis in a cirrhotic patient.

Septic arthritis is usually of hematogenous origin and is increasingly being reported in elderly patients, who often have underlying medical conditions such as diabetes or alcoholism. We report a 62-year-old patient with alcoholic liver disease who presented with Escherichia coli bacteremia and septic arthritis in a previously fractured ankle. There are scarce reports of infectious arthritis in cirrhotic patients, but this is the first report of arthritis after a primary enteric bacteremia. We believe that the patient described here developed E. coli bacteremia as a result of bacterial overgrowth and translocation related to alcoholic liver disease and cirrhosis. The resulting bacteremia resulted in the development of infection in the left ankle, which had preexisting disease and was thus vulnerable. This case provides further evidence for the mode of infection being bacteremia in cirrhotic patients. In patients with cirrhosis and fever, a high index of suspicion is required for joint infection as a potential cause of fever or deterioration in the cirrhotic's patient general condition.

The therapeutic effect of a combination of cofpropamine, a caffeine derivative, and cyclophosphamide on the development of adjuvant arthritis of rats and collagen arthritis of mice.

1. Cofpropamine (Cofa), a caffeine derivative that inhibits polyadenoribosylation, enhances the therapeutic effect of cyclophosphamide (CPA) in two animal models of arthritis. 2. The development of adjuvant arthritis of rats is reduced by treatment with 2 x 50 mg/kg IP CPA and 2 x 50 mg/kg IP Cofa. 3. The development of collagen arthritis in mice is prevented by treatment with 12.5 mg/kg IP CPA and 150 mg/kg IP Cofa three times per week.

Influence of diet free of NAD-precursors on acetaminophen hepatotoxicity in mice.

Recently, we demonstrated the hepatoprotective effects of nicotinic acid amide, a selective inhibitor of poly(ADP-ribose) polymerase (PARP; EC 2.4.2.30) on mice suffering from acetaminophen (AAP)-hepatitis, suggesting that the AAP-induced liver injury involves a step which depends on adenoribosylation. The present study investigates the effects of a diet free of precursors of NAD, the substrate on which PARP acts, in female NMRI mice with AAP hepatitis and evaluates the influence of simultaneous ethanol consumption in these animals. Liver injuries were quantified as serum activities of glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT). While AAP caused a 117-fold elevation of serum transaminase activities in mice kept on a standard laboratory diet, which was significantly exacerbated by ethanol and inhibited by nicotinic acid amide (NAA), adverse effects were noted in animals fed a diet free of precursors of NAD. In these animals, only minor increases of serum transaminase activities were measured in the presence of AAP, and unlike the exacerbation caused by ethanol in mice on a standard diet, the liver damage was inhibited by 50% by ethanol. A further 64% reduction of hepatitis was observed, when NAA was given to ethanol/AAP-mice. Our results provide evidence that the AAP-induced hepatitis and its exacerbation by ethanol can either be reduced by end-product inhibition of PARP by NAA or by dietary depletion of the enzyme's substrate NAD. We see the main application of NAA as for the combinational use in pharmaceutical preparations of acetaminophen in order to avoid hepatic damage in patients treated with this widely used analgesic.

The influence of antagonists of poly(ADP-ribose) metabolism on acetaminophen hepatotoxicity.

An array of therapeutically used analgetic and antirheumatic drugs causes severe liver damage. The present study investigates the hepatoprotective effects of inhibitors of NAD-dependent adenoribosylation reactions in analgesics-induced hepatic injury. Male NMRI mice were treated perorally with 500 mg/kg of acetaminophen, and the activities of both glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT) were determined in serum. In addition, the activity of poly(ADP-ribose)polymerase (PARP) was quantified in liver cell nuclei. While the PARP-activity remained essentially unchanged, the acetaminophen-induced release of both GOT and GPT from injured liver cells could be inhibited by 90-99%, when mice were injected additionally with the selective PARP-inhibitors nicotinic acid amide, benzamide, caffeine, theophyline, and thymidine, respectively. We see the main application of inhibitors of adenoribosylation reactions as for the combinational use in pharmaceutical preparations of analgesics and antirheumatic drugs in order to avoid hepatic damage.

The ergonomics of child care: conducting worksite analyses.

This paper examined the ergonomics of child care at a large metropolitan, university-based child care center. A case study approach was used to describe the job analysis process and results. Center staff were involved in the identification of health risk factors by completing an ergonomics survey and responding to questions posed during the job analysis (n=36). Two occupational therapists analyzed six different rooms, accommodating different age groups of children. Specific activities were identified as stressors and/or health risk factors inherent in the jobs according to the age of the children cared for. A list of ergonomic health risk factors and recommendations was generated.

Exacerbation of acetaminophen hepatotoxicity by thalidomide and protection by nicotinic acid amide.

1. The effects of racemic thalidomide (D[+]/L[-] alpha-phthalimido-glutarimide) on acetaminophen (AAP)-induced hepatitis were tested in male NMRI mice (n = 133) and quantified as serum activities of glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT). 2. A 2.1-fold increase of GOT and a 1.9-fold increase of GPT activities (P < 0.001) were observed in mice treated perorally with 500 mg/kg of AAP plus 150 mg/kg of thalidomide (Thal). In the absence of AAP, Thal did not display any detectable hepatotoxic effects. 3. The Thal-induced exacerbation of AAP hepatotoxicity was completely inhibited by nicotinic acid amide, a selective inhibitor of poly(ADP-ribose) polymerase (PARP) (P < 0.0001), suggesting a possible influence of Thal on the hepatic metabolism of NAD-adenoribosylation. 4. We see the main application of nicotinic acid amide as for the combinational use in pharmaceutical preparations of AAP in order to avoid hepatic damage in patients treated with AAP and Thal.

Health considerations for pregnant child care staff.

Child care is a profession comprised predominantly of young women of child-bearing age. Yet the pregnancy of child care staff has been discussed only incidentally in the health literature on early childhood. Because nursing professionals serve in a number of roles in child care centers, this is an important topic to include for health in-services and consultations. This article reviews what is currently known and recommended for pregnant child care staff regarding illnesses, stress, and the ergonomics of the job. The occupational health research that included women employed in child care is examined. Guidelines and recommendations for staying healthy and managing classroom activities during pregnancy are suggested.

School injuries: what we know, what we need.

Schools are the site of a substantial number of unintentional injuries each year. Current knowledge regarding the study of causes and implications of school injury is summarized in a review of the research literature. A discussion of future investigations and better management of school injuries focuses on research issues, practical management, and nursing concerns. Operational definitions and reporting mechanisms are emphasized as research needs. Practical management and nursing concerns include routine reporting, student supervision, treatment of injuries, communication with parents, and legal (liability) responsibilities.

[Personal experience with monitoring drug prescriptions in pregnancy]. / Nase zkusenosti s monitorováním preskripce léku v tehotenství.

The authors submit the results of an epidemiological perspective investigation concerned with drug prescription in 372 pregnant women during the period 1983-1988 in two municipal health communities of a regional town with an industrial and agricultural agglomeration. They record for orientation also some other factors which may have an impact on mother and foetus, i.e. smoking, alcohol intake, black coffee. In drugs with a possible negative effect on mother and foetus the prescribed dose was expressed in % DDD and the time interval during pregnancy. The results revealed a significant drop of drug prescription in all groups of drugs, in particular Ferronat, antihistaminic drugs and Diazepam. Perinatal complications, functional or somatic disorders in neonates were manifested in 31% of the total number of neonates. In the small group investigated by the authors neither the effect of the number of drugs nor a relationship between different drugs and certain functional or somatic disorders of the child during delivery were apparent.

Short time action of antirheumatic substances on the liver of rat. Protective effect of tryptophan + methionine.

1. A large number of drugs, including some antirheumatic substances, cause liver damage. 2. Only a little information is available, so far, on the causes of such damage and their prevention. 3. From studies on a number of antirheumatic drugs as to their effect upon the liver, three categories could be differentiated: (a) large effect (b) low effect (c) no effect. 4. Judging from our results, the liver damage is induced via a disturbance of the NAD-adenoribosylation metabolism.

Influence of oxypangam upon the induction of tyrosine aminotransferase, the NAD content and the ADPR transferase activity in several organs of the rat.

Oxypangam is a substance applied therapeutically against a number of diseases, such as chronic liver damages, angina pectoris, and psychosomatic disturbances. The mode of action of oxypangam has not yet conclusively been described. The only well-known properties of this substance are its intensive methylating and lipolytic effects. The present paper serves to elucidate the influence of oxypangam on the induction of the tyrosine aminotransferase, on the NAD content and on the activity of the ADPR transferase in the liver. Our studies showed that in normal animals, increasing doses of oxypangam support the induction of tyrosine aminotransferase. Up to a concentration of 100 mg/kg oxypangam enhances also the induction of tyrosine aminotransferase by tryptophan. In both cases, however, it does not work in adrenalectomized animals. Under the influence of oxypangam the NAD content of the liver remained unchanged, while the activity of the ADPR transferase was influenced only slightly.

Effects of altering dead space volume on respiration and air sac gases in geese.

Dead space volume (VD) was altered in spontaneously breathing, anesthetized geese from values far above (about 115 ml) to those far below (about 3 ml) the normal VD (approximately 40 ml). Respiratory gases were measured in cranial (CrS) and caudal air sacs (CdS) and in blood. The major findings were as follows: Ventilation increased linearly with VD, by increases in tidal volume (VT) at constant breathing rate (fresp); effective parabronchial ventilation, (VT-VD) X fresp, remained constant and so did arterial blood gases. No changes occurred in CrS gas composition. CdS PCO2 declined with decreasing VD, and the respiratory exchange ratio increased, reaching values above unity at the lowest VD. The gas composition in CrS, and particularly its relation to end-expired gas composition, is in agreement with current models of the gas flow pattern in the avian lung. The PCO2 values in CdS are higher than expected by simple models, e.g. by dead space re-inhalation. Neopulmonic gas exchange and incomplete gas mixing are suggested to contribute significantly to the gas composition of CdS.

Occupational therapy education: the relationship of purpose, objectives, and teaching models.

A clearly stated purpose of basic professional education in occupational therapy provides a base for educational programs to develop learning objectives and identify effective teaching models and behaviors. The primary purpose of professional education should be the development of problem-solving skills, self-awareness, and creative productive thinking, with "hands-on" skills relegated to a secondary purpose. Specific learning objectives and the teaching models that have been developed to meet these objectives are presented. The authors further suggest that there must be a relationship between what occurs in the classroom (implementation of teaching models) and the purpose of professional education. A survey of current occupational therapy faculty members was conducted to identify a) their preparedness in the use of teaching models and b) other factors affecting their classroom behavior (years of experience, educational level, area of concentration). Survey results portray a relatively young faculty in both rank and experience. Other data indicate that although 85% of the respondents had taken at least one education course, only slightly more than half were familiar with teaching models. Most respondents felt that course work in educational methods and models aids in the development of more effective teaching strategies.

Influence of streptozotocin upon the induction of tyrosine aminotransferase, the content of NAD and of 5-methyl cytosine in rat liver.

The antibiotic, streptozotocin, has carcinostatic, carcinogenic, and diabetogenic properties. Moreover, it is capable of inducing the enzyme tyrosine aminotransferase in a permanent line of rat liver cells. In the present publication, the effects of streptozotocin upon the induction of tyrosine aminotransferase, NAD synthesis, and methylation of DNA in different organs were analyzed in vivo. If administered alone, streptozotocin slightly induced tyrosine aminotransferase. The induction of tyrosine aminotransferase caused by tryptophan or nicotinamide was inhibited by streptozotocin. Streptozotocin reduced the NAD content of the liver. NAD synthesis induced by tryptophan was reduced by streptozotocin, while that induced by nicotinamide was enhanced. DNA methylation in the form of 5-methyl cytosine was not influenced by streptozotocin.

Influence of ethanol, nicotinamide, orotic acid and caffeine upon the induction of tyrosine aminotransferase, the NAD content and the ADPR transferase activity in rat liver.

Chronic uptake of ethanol leads to irreversible damage of liver cells. Until now the cause of this alteration is unknown. To get more information experiments presented in this paper were performed. Contrary to normal fed animals the enzyme tyrosine aminotransferase (TAT) can be induced by ethanol in starved rats. Orotic acid induces the TAT at a dose of 500 mg/kg. This effect is enhanced to some extent by ethanol. Ethanol increases the minor effect of 50 mg/kg caffeine on TAT induction markedly. Only 500 mg/kg nicotinamide (NA) enhances TAT activity. Here ethanol has a minor stimulatory effect. A combination of nicotinamide with orotic acid or with caffeine leads to substances with a higher effect on TAT induction. Besides nicotinamide and its derivatives only caffeine changes the NAD+ + NADH content of the liver. Ethanol and caffeine reduce the activity of the ADPR transferase. The results indicate that the effect of ethanol might be due to interference with NAD-adenoribosylation metabolism.

NAD metabolism and induction of tyrosine aminotransferase in the rat.

The relationship between the NAD-metabolism and the induction of the tyrosine aminotransferase was studied. The content of NAD+ + NADH differs markedly from organ to organ. The highest values can be found in the liver. In intact animals tryptophan leads to an increase of NAD in liver and kidney, but not in brain and spleen. Nicotinamide, on the other hand, induces NAD synthesis in all the organs tested. In adrenalectomized animals, however, there is practically no rise of the NAD content after application of tryptophan contrary to the effect of nicotinamide. The enzyme tyrosine aminotransferase can be induced in intact animals by nicotinamide and tryptophan. This effect is much less pronounced in adrenalectomized animals. In adrenalectomized animals the induction of the tyrosine aminotransferase by tryptophan is markedly elevated by caffeine and theophylline. Under these conditions there is a significant increase of the NAD content as well. The tryptophan promoted induction of the tyrosine aminotransferase is influenced by inhibitors of the ADPR-transferase. The data presented give further evidence that the NAD adenoribosylation metabolism is involved in the induction of the tyrosine aminotransferase.

Influence of ethanol upon the introduction of tyrosine aminotransferase in liver, upon the NAD content in liver and brain, and upon the activity of glutamate oxalate aminotransferase and glutamate pyruvate aminotransferase in the serum of rats.

The influence of ethanol, tryptophan, nicotinamide and methionine upon the activity of glutamate oxalate aminotransferase and glutamate pyruvate aminotransferase in serum as well as the induction of tyrosine aminotransferase in the liver, and of NAD+ + NADH in liver and brain are described. After oral application of 6 g/kg ethanol, the activities of the examined enzymes and the concentrations of NAD+ + NADH in the brain as well as in the liver did not change over a period of 8 hr. Administration of L-methionine lead--as is the case with DL-tryptophan--to a decrease of the NAD+ + NADH-concentration in the brain. A simultaneous application of nicotinamide, DL-tryptophan, L-methionine of l-methylnicotinamide together with ethanol caused a significant increase of the tyrosine aminotransferase induction in adrenalectomized animals. Ethanol reduced the activity of the ADPR transferase in the nuclei of rat liver cells.