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Biomedical subjects

W Stahl

Publications and source records attributed to W Stahl.

At least 19 recordsLinked to original sources
PubMed1992

Antioxidant functions of vitamins. Vitamins E and C, beta-carotene, and other carotenoids.

Tocopherols and tocotrienols (vitamin E) and ascorbic acid (vitamin C) as well as the carotenoids react with free radicals, notably peroxyl radicals, and with singlet molecular oxygen (1O2), this being the basis of their function as antioxidants. RRR-alpha-tocopherol is the major peroxyl radical scavenger in biological lipid phases such as membranes or low-density lipoproteins (LDL). L-Ascorbate is present in aqueous compartments (e.g. cytosol, plasma, and other body fluids) and can reduce the tocopheroxyl radical; it also has a number of metabolically important cofactor functions in enzyme reactions, notably hydroxylations. Upon oxidation, these micronutrients need to be regenerated in the biological setting, hence the need for further coupling to nonradical reducing systems such as glutathione/glutathione disulfide, dihydrolipoate/lipoate, or NADPH/NADP+ and NADH/NAD+. Carotenoids, notably beta-carotene and lycopene as well as oxycarotenoids (e.g. zeaxanthin and lutein), exert antioxidant functions in lipid phases by free-radical or 1O2 quenching. There are pronounced differences in tissue carotenoid patterns, extending also to the distribution between the all-trans and various cis isomers of the respective carotenoids. Antioxidant functions are associated with lowering DNA damage, malignant transformation, and other parameters of cell damage in vitro as well as epidemiologically with lowered incidence of certain types of cancer and degenerative diseases, such as ischemic heart disease and cataract. They are of importance in the process of aging. Reactive oxygen species occur in tissues and cells and can damage DNA, proteins, carbohydrates, and lipids. These potentially deleterious reactions are controlled in part by antioxidants that eliminate prooxidants and scavenge free radicals. Their ability as antioxidants to quench radicals and 1O2 may explain some anticancer properties of the carotenoids independent of their provitamin A activity, but other functions may play a role as well. Tocopherols are the most abundant and efficient scavengers of peroxyl radicals in biological membranes. The water-soluble antioxidant vitamin C can reduce tocopheroxyl radicals directly or indirectly and thus support the antioxidant activity of vitamin E; such functions can be performed also by other appropriate reducing compounds such as glutathione (GSH) or dihydrolipoate. The biological efficacy of the antioxidants is also determined by their biokinetics.

Animals↗
PubMed1992

cis-trans isomers of lycopene and beta-carotene in human serum and tissues.

Since cis or trans isomers of carotenoids may have different biological reactivities, the isomeric composition of lycopene and beta-carotene was measured in serum and seven human tissues. In addition to all-trans lycopene, at least three cis-isomers (9-, 13-, and 15-cis) were present, accounting for more than 50% of total lycopene. 13- and 15-cis-beta-carotene, however, were present at only 5% of the all-trans isomer. In addition, 9-cis-beta-carotene was present in tissue samples but not in serum. There were interindividual differences in carotenoid levels of the different tissue types, but liver, adrenal gland, and testes always contained significantly higher amounts of the carotenoids than kidney, ovary, and fat; carotenoids in brain stem tissue were below the detection limit. beta-Carotene was the major carotenoid in liver, adrenal gland, kidney, ovary, and fat, whereas lycopene was the predominant carotenoid in testes.

Adipose Tissue↗
PubMed1992

Uptake of lycopene and its geometrical isomers is greater from heat-processed than from unprocessed tomato juice in humans.

Lycopene and beta-carotene are the most abundant carotenoids in human blood and tissues. Although lacking provitamin A activity, lycopene may be biologically active by contributing to the antioxidative defense system of the organism. We studied the uptake of lycopene from processed (boiled with 1% corn oil for 1 h) and unprocessed tomato juice in humans. Lycopene concentrations in human serum increased only when processed tomato juice was consumed. Lycopene uptake varied with individuals, but peak serum concentrations were always reached between 24 and 48 h. The carotenoid was eliminated from serum with a half-life of 2-3 d. The increase in peak serum concentrations was dose-dependent but not linear with the dose. Repeated doses led to a continual rise of lycopene in human serum. Of the different geometrical isomers (all-trans, 9-cis and 13-cis), the cis isomers seemed to be somewhat better absorbed than the all-trans form.

Absorption↗
PubMed1992

Guaiac testing in the diagnosis of rectal trauma: what is its value?

Rectal examination with guaiac testing is a standard part of the emergency department evaluation of acutely traumatized patients. Its major role is in the recognition of occult bowel injury. We questioned its efficacy in detecting occult rectal injury in patients with penetrating trauma. We reviewed the charts of 19 patients with suspected rectal injury. Ten injuries were to the abdomen, nine to the buttock, and three to the thigh. Guaiac testing was 69% (11/16) sensitive and 33% (1/3) specific. Rigid sigmoidoscopy was 100% (12/12) sensitive and 67% (2/3) specific. Sensitivity was 100% (8/8) when the two were combined. Our findings suggest that guaiac testing is not accurate enough to rule out the presence of occult rectal injury. The result of guaiac testing must not influence the decision to further evaluate patients with high-risk injuries.

Adult↗
PubMed1991

Comparative study on the influence of two 2-chloroethylnitrosoureas with different carbamoylating potential towards glutathione and glutathione-related enzymes in different organs of the rat.

The influence of two CNUs with similar alkylating but strongly different carbamoylating activity towards the glutathione system was investigated in different organs. Both CNUs influence the glutathione system of the bone marrow in a similar manner, irrespective of their carbamoylating potential. In contrast, glutathione reductase activity in the other organs was strongly decreased by the potent carbamoylator BCNU, whereas no or only minor effects were produced by its weakly carbamoylating counterpart HECNU. The results confirm that bone marrow toxicity of CNUs primarily results from alkylation and not from carbamoylation. Other organ-related toxic effects, however, are probably a result of carbamoylating reactions exerted by BCNU. This applies especially to lung toxicity that has been observed frequently as a major side effect in clinical trials with BCNU.

Alkylation↗
PubMed1989

Indications for barium enema preceding colostomy closure in trauma patients.

The need for a barium enema (BE) preceding colostomy closure is controversial. In the process of evaluating the usefulness of BE before closure of colostomies performed for colorectal injuries, we reviewed our experience with 84 trauma patients who underwent BE before colostomy closure. Patients who had their colonic injuries repaired or diverted during the initial procedure did not benefit from the precolostomy closure contrast study. In this group of patients artifacts on BE had to be ruled out by endoscopy or repeat radiography in 9.5% of patients. Barium enema was found beneficial in evaluating colorectal injuries below the peritoneal reflection in one out of 20 patients. However, since the rectal injuries are not usually explored and repaired during the initial procedure, investigation by endoscopy and contrast studies may still be indicated preceding colostomy closure.

Adolescent↗
PubMed1989

Nitrosoureas. Modes of action and perspectives in the use of hormone receptor affinity carrier molecules.

Mechanisms of DNA adduct formation by antineoplastic 2-chloroethyl-N-nitrosoureas (CNUs) and of DNA damage induced by these compounds are discussed. CNUs are alkylating agents that form DNA-DNA cross-links as well as 2-chloroethylated and 2-hydroxyethylated adducts, the N-7-position of guanine being the predominantly alkylated site. A close correlation exists between the potential of a given compound to induce DNA-DNA cross-links and its antineoplastic effectiveness. However, levels of DNA-DNA cross-linking in bone marrow and extent of myelosuppression as measured in rodents are also closely correlated. The design of new cross-linking analogues capable of directing the antineoplastically relevant activity predominantly to the target tumour appears therefore to be of great promise. Cross-linking agents have been attached to a variety of steroid hormone carrier molecules and the conjugates have been tested in structure-activity studies using hormone-receptor containing animal tumours. These studies have revealed that some hormone-linked antineoplastic agents are highly effective in receptor positive experimental tumours and are superior to mixtures of unlinked alkylating agents with hormones. Indications for a relative enrichment of DNA damaging effects in the tumour tissue and for reduced myelotoxicity have been obtained with specific hormone conjugates.

Animals↗
PubMed1988

Regional differences in hindgut structure and function in the nutria, Myocastor coypus.

Morphologically the large intestine of the nutria resembles that of other caviomorphs, notably the guinea pig. The cecum is voluminous: it contributes 8.6% of the total intestinal length and 12.7% of the total intestinal surface area (considering the surface enlargement factor). It contains 27-32% of the wet ingesta and 20-23% of the dry matter in the gastrointestinal tract. In the colon the corresponding figures are: 21.8% of length, 12.6% of surface area, 16-21% of wet ingesta, and 16-40% of dry matter. The colon can be subdivided both structurally and functionally into two sections, the proximal and the distal colon, the border between the two being the apical flexure of a long parallel loop. The proximal colon (42% of colonic length) displays on the mucosal surface of its mesenterial side a narrow furrow bordered by ridges, which is absent in the distal colon. The ridges contain subepithelial accumulations of coiled tubuloalveolar mucoid glands, entwined by bundles of muscle fibers. Determinations of nitrogen in the contents near the furrow suggest a concentration of bacteria in this part of the lumen. It is hypothesized that the structural differentiations of the proximal colon provide mechanisms for the transport of bacteria from the proximal colon back into the cecum to maintain the fermentation function. The slopes of the longitudinal profiles for dry matter and for concentrations of sodium, potassium and calcium in the luminal contents change at the tip of the parallel loop. The electrical potential difference "intestinal lumen - blood" is particularly large in the proximal colon, indicating active electrogenic ion transport in this region.

Animal Nutritional Physiological Phenomena↗
PubMed1988

Influence of glutathione on the mutagenicity of 2-chloroethylnitrosoureas. Mutagenic potential of glutathione derivatives formed from 2-chloroethylnitrosoureas and glutathione.

2-Chloroethylnitrosoureas (CNU) are antineoplastic agents whose therapeutic dose is limited by toxic and carcinogenic side effect. The clinically used drugs, bis-(2-chloroethyl)nitrosourea (BCNU) and 1-(2-chloroethyl)-3-(2-hydroxyethyl)-1-nitrosourea (HECNU) and their analogue N-(2-chloroethyl)-N-nitrosocarbamoyl-glycinamide (CNC-GA) were tested for mutagenicity and toxicity in the Salmonella typhimurium tester strain TA1535 in the presence and absence of glutathione (GSH). All 3 compounds proved to be potent mutagens. The cytotoxicity of these CNUs, however, varied depending on their carbamoylating activity. These cytotoxic effects were decreased considerably by the addition of GSH. It has been shown that the isocyanate decomposition product of the 2-chloroethylnitrosoureas reacts with GSH yielding S-carbamoylated GSH derivatives. The adducts resulting from coincubation of BCNU or HECNU with GSH, 2-chloroethyl-S-carbamoyl-GSH and 2-hydroxy-S-carbamoyl-GSH, were also tested for their mutagenic activity. While the hydroxyethylated compound exhibited no effects, 2-chloroethyl-S-carbamoyl-GSH and its cysteine analogue, 2-chloroethyl-S-carbamoyl-GSH, were strong mutagens. Further experiments with 3-chloropropyl-S-carbamoyl-GSH and t-butyl-S-carbamoyl-GSH indicate that a chlorine substituent in the beta position is necessary for the induction of a potent mutagenic response.

Carmustine↗
PubMed1988

Chronic murine toxoplasmosis: clinicopathologic characterization of a progressive wasting syndrome.

Nya:NYLAR albino mice infected with Toxoplasma gondii gradually developed a chronic and progressive wasting syndrome characterized by facial and body alopecia, corneal opacities, necrotic lesions of ears and tail, signs of neurologic disease and death within six to eight months after infection. Haematologic changes included a transient normochromic, normocytic anaemia, and persistent lymphopenia and neutrophilia. Changes in serum proteins were manifested by hypoalbuminaemia and pronounced hypergammaglobulinaemia. Serum thyroxine concentrations fell sharply during the first month of infection, then gradually returned to control concentrations. Gross changes included loss of body weight, hepatosplenomegaly, ovarian and uterine atrophy, and a marked involution of the thymus. The predominant histopathologic change in the brain was a mononuclear cell vasculitis, particularly affecting the hippocampus and the choroid plexus, ependyma, and periventricular areas of the lateral and third ventricles. These preliminary observations indicate that mice can serve as a practical animal model of great potential for study of the pathogenesis of chronic toxoplasmosis.

Animals↗
PubMed1988

Selective conservatism in abdominal stab wounds: the efficacy of serial physical examination.

An analysis of 186 consecutive patients with anterior abdominal stab wounds in a 2-year period was carried out to assess the efficacy of serial physical examination as the determining factor for the need for laparotomy. Of 106 patients managed by clinical evaluation, the incidence of negative laparotomy was 0.9% and three patients (2.7%) had an "unnecessary" celiotomy. There were no missed injuries or delayed detection of intraperitoneal visceral trauma. The incidence of negative laparotomy among patients subjected to wound exploration +/- peritoneal lavage (n = 41) was 2.4%, and 39 patients had mandatory laparotomy for evisceration, with a negative celiotomy rate of 20.5%. Our experience supports serial physical examination as a highly effective method of "selective conservatism" of anterior abdominal stab wounds. Mandatory laparotomy for evisceration needs further clarification.

Abdominal Injuries↗
PubMed1987

A method to determine the carbamoylating potential of 1-(2-chloroethyl)-1-nitrosoureas.

1-(2-Chloroethyl)-1-nitrosoureas (CNUs) are alkylating agents that also possess carbamoylating activity, depending on the chemical nature of the substituent at N-3. Although effects on a variety of enzymes, including inhibition of glutathione reductase (GS-R) have been attributed to carbamoylation, the biological significance is still not well understood. This deficiency is due at least in part to the analytical method that has been used to measure carbamoylation:in-vitro reaction with the omega-amino group of lysine. Reaction of CNUs with glutathione (GSH) offers a better estimation of carbamoylating potential in vitro. The decrease in free thiol groups during incubation of GSH with various CNUs can be followed using the thiol reagent 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB). With this test, carbamoylating potential relative to that of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) as 100% was 94% for 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (MeCCNU), 86% for 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), 16% for 1-(2-chloroethyl)-3-(2-hydroxyethyl)-1-nitrosourea (HECNU) and 6% for chlorozotocin (CLZ). Various carbamoylated and alkylated GSH derivatives, such as S-(2-chloroethylcarbamoyl)-, S-(2-hydroxyethylcarbamoyl)-, S-(cyclohexylcarbamoyl)-, S-(4-methylcyclohexylcarbamoyl)- and S-(2-hydroxyethyl)glutathione, are formed on incubation of GSH with CNUs. High-performance liquid chromatography (HPLC) revealed that, in comparison to carbamoylated compounds, alkylated GSH derivatives are formed in only low yields (less than 3%). Formation of carbamoylated products during incubation correlated with the decrease in free thiol groups. Concentrations achieving 50% GS-R inhibition in vitro were 0.16 mM for BCNU and 1.9 mM for HECNU.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkylating Agents↗
PubMed1987

Penetrating thoracic injuries: in-field stabilization vs. prompt transport.

One hundred patients who were in extremis and required Emergency Room Thoracotomy (ERT) after sustaining penetrating thoracic injuries were analyzed to compare the results of attempted stabilization in the field (n = 51) with those who had immediate transportation (n = 49). The clinical status of the patients in the field and in the E.R. was quantified by Trauma Score (TS) as well as Physiologic Index (PI), ranging in severity from 20 (clinically dead) to 5 (stable). The anatomic injury severity was expressed by Penetrating Trauma Index (PTI). Survival was analyzed according to the type of injuries: noncardiac and cardiac. The overall survival was 10%. There was only one survivor with noncardiac injuries. Sixty-nine patients had cardiac penetration, 33 in Group I (stabilization) and 36 in Group II (immediate transport). Despite attempts at stabilization, none of the patients in Group I showed an improvement in clinical status from the scene to the emergency room. There were a higher number of patients arriving at the E.R. with signs of life in Group II compared to Group I. In Group II patients, survival was significantly improved overall (p = 0.01), in patients with signs of life on arrival at the hospital (p = 0.02) and in patients with isolated right ventricular wounds (p = 0.01) compared with Group I. The anatomic injury severity (PTI) as well as the mode of injury in the two groups was similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Emergency department thoracotomy for penetrating injuries: predictive value of patient classification.

In 18 months, 44 patients underwent thoracotomy in an emergency department (ED) for penetrating thoracic injuries. Of 14 patients resuscitated, seven (50%) survived, and all were neurologically intact. Patients were classified according to the quality of signs of life in transit or upon arrival at the ED. Identical survival rates of 29% were noted for patients in Group I (profound shock) and in Group II (agonal), with survival at 14% for individuals in Group III ("dead" on arrival). There were no survivors among patients in Group IV ("dead" on the scene), and ED thoracotomy, in the authors' opinion, is fruitless in this group. In Groups I, II, and III, total salvage from cardiac injuries was six of 24 patients (25%), and for those with non-cardiac injuries, it was one of 11 (9%). The rate of survival from cardiac stab wounds in Groups I, II, and III, was five of 16 (31%) and one of eight (13%) for gunshot wounds. Five of the seven survivors (71%) arrived at the ED by rapid transport without the benefit of any pre-hospital life support. Patient classification appears to be a valuable tool in evaluating the benefit of ED thoracotomy. The neurological status of all survivors and pertinent transportation data should be included in all future studies of ED thoracotomy. "Scoop and run" in the urban setting with rapid transport capability may be superior to pre-hospital stabilization of victims of penetrating thoracic trauma.

Adolescent↗
PubMed1986

Drug design: nitrosoureas.

Attempts to develop more effective and less toxic antineoplastic nitrosoureas are summarized. Previous research resulted in the synthesis and extensive preclinical testing of new, short-chain, water-soluble, but lipophilic compounds--1-(2-chloroethyl)-1-nitroso-3-(2-hydroxyethyl)urea (HECNU) and 1-(2-chloroethyl)-1-nitroso-3-(methylene carboxamido)urea. Molecular mechanisms of reactions with biomolecules are discussed with regard to DNA alkylation and cross-linking, carbamoylation of glutathione and glutathione reductase inhibition. Results of a clinical phase-II study show that HECNU, as predicted from preclinical tests, exhibits outstanding activity in brain tumours. Future development concentrates on the use of carrier molecules for nitrosoureas. Results of an extensive structure-activity study with oestradiol-linked analogues show that an oestradiol-17 ester derivative is much more active than other analogues.

Alkylating Agents↗
PubMed1985

Responses of opsonic substances to major trauma and sepsis.

Adequate opsonic capability is vital for normal host defense against infection. The presence of complement fraction 3 (C3) indicates both classical and alternative pathways of complement activation, while complement fraction 4 (C4) indicates only classical pathway activation. C-reactive protein (CRP) functions as an opsonic substance. We measured serum levels of C3, C4, and CRP in 32 trauma patients. Six suffered minor injuries and 26 suffered major injuries. Nineteen of the major-injury patients developed post-trauma sepsis. Complement levels fell immediately after injury and remained low for approximately 8 days in all patients. CRP levels rose by 12 h, peaked at 48 h, and correlated with the severity of injury and the presence of sepsis. Elevated CRP levels after 4 days postinjury indicated the presence of sepsis in all cases. CRP elevations preceded clinical diagnosis by an average of 2.4 days. Serial measurements of CRP are valuable in monitoring the course of trauma patients and may indicate the presence of septic complications before clinical detection.

C-Reactive Protein↗
PubMed1985

Hypothalamic-adenohypophyseal origin of reproductive failure in mice following chronic infection with Toxoplasma gondii.

Mice chronically infected with Toxoplasma gondii exhibited reproductive failure characterized by a constant diestrous vaginal cytology and ovarian and uterine atrophy. Chronically infected mice were treated with 20 ng of D-Leu6-des-Gly-NH2-Pro-ethylamide (D-Leu6), a structural analog of luteinizing hormone-releasing hormone (LHRH), every 4 hr over a 12-hr period daily, for 3 days. Infected animals treated with D-Leu6 had greater pituitary weight (P less than 0.01), ovarian weight (P less than 0.01), and uterine weight (P less than 0.025), than did infected control mice treated with saline. In addition, a change in vaginal cytology to estrus, metestrus, and proestrus of the D-Leu6-treated animals was observed, although a contiguity of normal estrous cycles and reproductive function was not determined. Comparable basal levels of serum luteinizing hormone (LH) were seen in infected mice and uninfected normal mice. However, the infected animals demonstrated a decreased pituitary responsiveness to D-Leu6 when monitored at 60 (P less than 0.025) and 120 min (P less than 0.010) following intraperitoneal administration of a bolus of 200 ng of the analog. Thus, the observed reproductive failure involves the readily releasable pool of pituitary LH, since basal LH is similar in both groups, and appears to be due to a dysfunction of the hypothalamic-adenohypophyseal axis.

Animals↗