Salutary effects of tachykinin receptor antagonists in a rat model of postoperative ileus.

BACKGROUND: Postoperative ileus (PI) is a common surgical complication treated mainly with supportive measures. Tachykinins control gastrointestinal motility and modulate somatic and visceral pain sensation; therefore, the effect of tachykinin receptor antagonists in a rat model of PI using NK(1-3) antagonists, SR140333, SR48968, and SR142801, was investigated. MATERIALS AND METHODS: Intestinal transit was measured as Evans blue migration after varied nociceptive stimuli: skin incision (SI), laparotomy (LAP), or laparotomy plus gut manipulation (L + M) in anesthetized rats. RESULTS: Diethyl ether anesthesia and SI did not influence the intestinal transit of the dye in comparison to untreated animals--UN: 61.17 +/- 5.47, 62.10 +/- 8.30, and 56.70 +/- 4.10 cm, respectively. In contrast LAP and L + M have significantly reduced intestinal motility to 26.40 +/- 2.07 and 9.70 +/- 1.15 cm, respectively. SR140333 (3-30 microg/kg), SR48968 (1-30 microg/kg), and SR142801 (3-10 microg/kg) reversed the additional inhibitory effects of gut manipulation subsequent to LAP dose-dependently, the dye transit returning with the use of the most effective antagonist doses up to 25.28 +/- 1.08, 21.70 +/- 0.19, and 25.0 +/- 1.34 cm. The combinations of submaximal doses of NK(1) and NK(3), NK(2) and NK(3) and NK(1), and NK(2) and NK(3) antagonists were not more effective than a single-agent regimen. On the other hand SR140333 and SR48968 (NK(1) + NK(2) antagonists) acted additively, the intestinal transit reaching 26.60 +/- 0.85 cm. SR140333, SR48968, and SR142801 have not affected the intestinal passage in UN rats or those undergoing SI or LAP. CONCLUSIONS: SR140333, SR48968, and SR142801 exert a salutary action on suppressed gut motility following surgical manipulation of the gut, the combination of NK(1) and NK(2) antagonists being most beneficial.

The role and interactions of nitric oxide (NO), carbon monoxide (CO), and prostanoids in the pathogenesis of postoperative ileus in rats.

The effects of heme oxygenase (HO) inhibitors, zinc-protoporphyrin-IX (ZnPP-IX), and tin protoporphyrin-IX (SnPP-IX) and their interactions with L-arginine/nitric oxide synthase (NOS) and cyclooxygenase (COX) pathways were investigated in postoperative ileus in rats. Intestinal transit was measured as Evans blue migration after skin incision, laparotomy or laparotomy plus gut evisceration and handling. Laparotomy and small intestinal manipulations increased blood plasma nitrites/nitrates level 1.88-fold. N(omega)-nitro-L-arginine methyl ester, indomethacin, a selective COX-1 blocker (resveratrol) and COX-2 antagonists (nimesulide, DuP-697, NS-398) reversed the additional inhibitory effects of gut manipulation subsequent to laparotomy. In contrast, N-(3-(aminomethyl)benzyl)acetamidine or S-methylisothiourea, highly selective inducible NOS blockers, remained ineffective. ZnPP-IX and SnPP-IX overturned the effects of laparotomy on dye propulsion, but were only partially effective after laparotomy and gut handling attenuating the additional inhibitory influences of gut manipulation, the intestinal transit reaching 89.21%, 92.87%, 53.46%, and 48.56% of respective controls transit. Salutary effects of L-NAME, ZnPP-IX, and SnPP-IX were dose-dependent, L-arginine or hemin (HO substrate) sensitive. Administration of indomethacin and resveratrol subsequent to SnPP-IX reversed the inhibitory effects of laparotomy and manipulation, amounting to 93.91% and 87.43% of controls. On the other hand, L-NAME injected after SnPP-IX abolished the salutary effects of the latter, study dye migration reached 25.18% of control rat. Therefore we demonstrated that nitric oxide, carbon monoxide, and prostanoids play a role in the pathogenesis of postoperative ileus albeit in different mechanisms. Laparotomy stimulated HO activity, whereas gut manipulation led to an excessive constitutive NOS stimulation accompanied by augmented prostanoid synthesis by COX-1. Unaffected synthesis of either NO or CO enables a return of gastrointestinal transit during postoperative period, whereas a pharmacological blockade of two complementary metabolic pathways provides a most effective measure against postoperative ileus development.

Full-size form of human liver AMP-deaminase?

AMP-deaminase from human liver was purified by two-step phosphocellulose chromatography, and SDS-PAG electrophoresis of the most active enzyme fraction eluted has been performed. The largest of the protein fragments revealed had a size (92 kDa) of an apparent full-size enzyme subunit, and reacted positively with antibodies produced against specific human ampd2 gene product. Three-day storage at cold room temperature modified significantly the electrophoretical pattern of the enzyme, evidencing continuous and progressive degradation of its structure. This is a first report evidencing the presence of apparent full-size form of human liver AMP-deaminase in preparation obtained from endogenous source.

[Gene therapy in chronic heart failure--hopes and fears]. / Terapia genowa w przewleklej niewydolnosci serca--nadzieje i obawy.

The article presents current views on the possibility of the applying of the gene therapy for advanced heart failure treatment. The gene therapy which offers a completely new treatment of this disease, but it requires a lot of many further efforts in development of gene-transfer vectors, gene-delivery techniques and new target genes identification.

[Evaluation of illicit drug use among students from universities in Gdansk]. / Ocena uzywania srodków uzalezniajacych przez studentów wyzszych uczelni Gdanska.

Anonymous questionnaire examinations were performed among 1585 students from eight universities in Gdansk, including 664 men and 921 woman from 17 to 48 (mean 21.4 +/- 2.26) years old. Illicit drugs were used by 45.9% of them, including 33.7% applying sporadically. Since a large group of respondents (approx. 24%) used from two to seven narcotics, frequency of students' contacts with different narcotics, given below, was altogether higher than 45.9%. Women significantly less frequently than men were taken two or more illicit drugs (chi 2 = 69.4; p < 0.0001). Cannabis was used by approx. 41% respondents (including about 29.8% applying sporadically), amphetamine by about 11% (including about 7.4% applying sporadically), LSD and magic mushrooms approx. 3.7% each, cocaine 1.1%. A few students took opium alkaloids, ecstasy, jimson-weed, and peyote. Men applied illicit drugs significantly more often than women did (chi 2 = 65.16; p < 0.0001). Drug addicted students (approx. 1.4%) smoked more cigarettes and drunk more alcohol. The frequency of illicit drugs use was the highest among students from Academy of Fine Arts (about 70%), University School of Physical Education (about 58%) and Gdansk University (about 49%). Respondents of Priest Seminary have had no contacts with narcotics.

[The evaluation of smoking and alcohol consumption by university students in Gdansk]. / Ocena nikotynizmu i picia alkoholu przez studentów wyzszych uczelni Gdanska.

Anonymous questionnaire examination were performed among 1585 students from eight universities in Gdansk, including 664 men and 921 women from 17 to 48 (mean 21.4 +/- 2.26) years old. Alcohol was consumed by 1452 (91.61%) students, including 91.53% women and 91.72% men. Both men and women preferred beer, respectively, 73.7% and 50.6%. In three-stage AUDIT-test (alcohol drinking dangerous to health) including 716 (45.2%) students, most of them in stage A (81.6%); in stage B about 8.2% comprised while there were about 10.2% in stage C students. Alcohol consumption carried the lowest risk (stage A) among students of Medical University while corresponding risk was the highest among students of Maritime High School. Among respondents drinking alcohol dangerously to health there were significantly more persons who did drugs (73.7%). Students qualified to the AUDIT test smoked cigarettes significantly more often than the rest of the examined population. Smokers amounted to 399 (25.2%) students, including 224 (26.3%) women and 157 (23.6%) men. The difference in figures was statistically non-significant. Among smoking respondents the students of Fine Arts Academy constituted the majority, while those of Medical University and of University School of Physical Education were in minority. Catholic Priest Seminary respondents did not have the relevant experiences.

[Criminal contamination by metallic mercury of cow's silage]. / Kryminalne skazenie rtecia metaliczna paszy dla krów.

This paper presents an unsuccessful homicidal attempt on 23 persons by means of metallic mercury added in large amount to cow's silage. Thirteen adults and twelve children used milk from these cows for 4.5 months. The mercury concentration in the milk of these cows as well as in serum and daily urine of consumers of the milk were examined by atomic absorption spectrophotometry. Despite the increased level of mercury in the milk (average 0.023 mg/kg), the concentrations of mercury in daily urine of only three persons were raised about 50%. These people had been working in a cowshed without ventilation every day for many months and thus had been exposed to vaporised mercury.

[The evaluation of methods of usage of addictive substances among high school students and Gdansk University students]. / Ocena uzywania srodków uzalezniajacych przez mlodziez wybranych szkól srednich i studentów Akademii Medycznej w Gdansku.

Anonymous questionnaire examination was performed among 222 high school pupils and 301 students of Gdansk Medical University, including 210 men and 313 women from 18 to 35 (mean 20.8 +/- 2.56) years old. Marijuana was used by 31.2% of them (once a week or more often 3.82%), amphetamine and Ecstasy by 9.4% (once a week or more often 1.52%), LSD by 3.8%, hallucinogenic mushrooms by 3.1%. Opium alkaloids, peyotl, jimsonweed were taken by a few pupils. The frequency of the drugs usage was significantly higher among school pupils (42.8%) than among Medical University students (30.2%) (chi 2 = 8.80; p < 0.003). Men applied drugs about twice as often as women and the difference was as well statistically significant (chi 2 = 12.95; p < 0.0003). 29.5% men and 25.2% women were cigarette smokers, but only in more advanced smokers (5 cigarettes and more per day) there was a significant difference between male and female (chi 2 = 8.69; p < 0.004).

[Acute ethanol and drug poisoning in alcohol abusers]. / Ostre zatrucia etanolem i lekami u osób uzaleznionych od alkoholu.

In the period from 1997 to 1999 one hundred twenty one alcohol abusers were admitted to the clinic with acute ethanol and drug poisoning, including 95 men and 26 women from 18 to 69 (mean 36) years old. Fifty eight persons were poisoned by ethanol, in remaining 63 cases intoxications were mixed e.g. including benzodiazepines, tricyclic antidepressants, carbamazepine, amphetamine, phenothiazines, barbiturates, theophylline, salicylates. In the mixed poisonings group two men (3.2%) died at the age above 50 years old suffering from congestive heart failure, bronchopneumonia and ventricular fibrillation. In the ethanol intoxication group there was no fatal case.

[Fatal ethanol poisoning of the alcohol abusers]. / Smiertelne zatrucie etanolem osób uzaleznionych od alkoholu etylowego.

The examined cohort consisted of 137 alcohol abusers, who died suddenly because of the acute ethanol poisoning. Among them there were 109 men and 28 women from 25 to 73 (mean 46.3 +/- 9.22) years old. Autopsy examinations performed in Department of the Forensic Medicine revealed no traumas or diseases explaining the sudden death, but showed the increased blood ethanol concentration from 3.6 to 8.8 (mean 4.67 +/- 0.74) g/l and urine ethanol concentration from 2.0 to 7.3 (mean 4.88 +/- 0.87) g/l. In the period 1996-1999 in Gdansk Province there was twofold decrease in the number of sudden death caused by the acute ethanol poisoning in the alcohol abusers.

[Intravenous self-administration of metallic mercury by two alcohol abusers]. / Dwa przypadki dozylnego wstrzykniecia rteci metalicznej u osób uzaleznionych od alkoholu.

This paper presents two alcohol abusers, who intravenously self-injected metallic mercury. In one of them during the injection a portion of mercury penetrated into extravenous compartment of his right arm. The second patient with depression, sociopathy and three suicide attempts in the past repeated intravenous injections with small amounts of mercury several times. The results of physical examination and all laboratory tests for both the men were normal. Blood mercury concentrations were 300 micrograms/l and 710 micrograms/l, respectively. X-ray film revealed the presence of metallic mercury deposits in lungs, right ventricle and inside the interstitial tissue of the right arm. The largest deposits of mercury inside and necrotic tissue were surgically removed from the right arm.

[Homocysteine as a risk factor for atherosclerosis]. / Homocysteina jako czynnik ryzyka rozwoju miazdzycy.

This article presents current views on the significance of homocysteine as a potential risk factor for atherosclerosis. The majority of numerous and extensive comparative examinations indicate that considerable hyperhomocysteinemia is an independent risk factor for the development of the premature atherosclerotic lesions. Because of that experts of the Nutrition Committee of American Heart Association published in 1999 the recommendations for the application of the preventive diet rich in vitamins B6, B12 and folic acid.

[Suicidal poisoning with tricyclic antidepressants]. / Samobójcze zatrucia trójpierscieniowymi lekami przeciwdepresyjnymi.

In the period from 1989 to 1998, 98 patients with suicidal tricyclic antidepressants poisoning were treated, including 47 men and 51 women from 16 to 74 (mean 35) years old. Thirty persons were poisoned by tricyclic antidepressants, in 68 remaining cases intoxications were mixed eg. including tricyclic antidepressants and benzodiazepines, phenothiazines, barbiturates, alcohol, amizepine, salicylates. The main causes of suicides were various kinds of depression (66%) as well as psychopathy and sociopathy (18%). Twenty patients attempted repeatedly to commit suicide. These were mainly patients suffering from endogenous depression, psychopathy and schizophrenia. In the examined group five patients died (5%) but three women out of them were aged, suffered from congestive heart failure and were poisoned with tricyclic antidepressants, benzodiazepines and barbiturates.

[Endothelins--their physiological role and their clinical significance]. / Endoteliny--ich rola fizjologiczna i znaczenie kliniczne.

Biochemical part of the paper presents the structure, biosynthesis and degradation of the endothelins. Physiological chapter deals with endothelin-1 endocrine and mitogenic action as well as its impact on diuresis, natriuresis and cardiovascular system. In the clinical part of the article the role of endothelin-1 in essential hypertension, congestive heart failure and chronic renal failure is described.

Subcutaneous self-injection and oral self-administration of metallic mercury--case report.

This paper presents a case of 16-year-old schoolboy who injected subcutaneously about 6 ml of metallic mercury to both forearms and administered orally about 5 ml of it. The patient was admitted to hospital two weeks after this incident without any clinical symptoms. Physical examination and all laboratory tests, including chest x-ray were unremarkable except for granulomata at the injection sites. X-ray examination showed numerous, dispersed globules of mercury in subcutaneous tissue of both forearms and in the digestive tract, mainly in the appendix. Granulomatous tissue with a part of mercury from both forearms as well as appendix were surgically removed. During a six-month period no toxic effects of mercury have been observed, in spite of the fact, that blood mercury level was 132 micrograms/L and urinary mercury level was 500 micrograms/L.

Acute poisoning with clenbuterol--a case report.

In the paper we have described a case of acute, unintentional intoxication with clenbuterol, a selective beta 2-agonist. A 21-year-old bodybuilder to improve his physical fitness and to increase his muscle bulk was using clenbuterol in a dose of two tablets (20 mg) daily for a week before poisoning. On a day of acute intoxication he drank orange juice containing 48 tablets (4.8 g) of clenbuterol, which had been placed there by his friends. The patient was admitted to our clinic with tachycardia at rate 160 bpm, headache, dizziness, tremor, sweats, muscle weakness, agitation. Serum potassium concentration was 2.6 mmol/L, blood glucose level 18.7 mmol/L. All the symptoms and biochemical abnormalities disappeared after intravenous treatment with propranolol (1.0 mg) and potassium chloride (60 mmol) within five hour period. This case indicates that more attention should be paid to clenbuterol widely used as a stimulant by athletes, especially by bodybuilders.

[Suicidal poisoning with benzodiazepines]. / Samobójcze zatrucie benzodiazepinami.

In the period from 1987 to 1996, 103 patients with suicidal benzodiazepines poisoning were treated, including 62 women and 41 men from 16 to 79 (mean 34) years old. 23 persons were poisoned only by benzodiazepines, in 80 remaining cases intoxications were mixed eg. including benzodiazepines and alcohol, tricyclic antidepressants, barbiturates, opioids, phenothiazines. The main causes of suicides were mainly depression, drug addiction and alcoholism. Nobody died in the benzodiazepines group, while mortality rate in the group of mixed poisoning was 4%. Prescribing benzodiazepines by physicians was quite often not justified and facilitated, among others, accumulation of the dose sufficient for suicide attempt. Flumazenil was efficient for leading out from coma in 86% of cases with poisoning only by benzodiazepines and 13% of cases with mixed intoxications mainly containing benzodiazepines and alcohol or carbamazepine.