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.

Increased potency of some substituted short peptide analogues in comparison to galanin(1-15)-NH(2)in rat fundus strips.

The activity of short porcine galanin (Gal) analogues was tested in vitro using rat gastric fundus strips. The peptides contracted longitudinal smooth muscle in a concentration-dependent manner with the following order of potency: Gal(1-29) >[Cit(14)]Gal(1- 15) >[Asp(14)]Gal(1- 15) >[Dab(14)]Gal(1- 15) >[Nle(14)] Gal(1-15) >[Dpr(14)]Gal(1- 15) >[Arg(14)]Gal(1- 15) >[Orn(14)]Gal(1- 15) >Gal(1-15). Only in the case of two peptides, namely [Cit(14)]Gal(1-15) and [Dab(14)]Gal(1-15) did the values of Hill coefficients, estimated from the appropriate concentration-contraction curves, differ significantly from unity. Our results indicate that both N- and C-terminals of Gal molecule contribute towards the affinity and activity of Gal in rat gastric smooth muscle cell receptors, indicating that their integrity is essential for its full excitatory myogenic action. The substitution of histidine with citruline, aspartic acid, norleucine or diaminobutyric acid in position 14 of the amino acid chain led to a considerable increase in potency, suggesting that amino acids located at this position might play a crucial role where the strength of short analogues is concerned.

[Methotrexate--mechanism of action and application]. / Metotreksat--mechanizm dzialania i zastosowanie.

The paper present modern views on turnover, mechanism of action and application of methotrexate. Contraindications and the most frequent side effects observed in certain number of patients treated with this drug are discussed.

Perifolliculitis capitis abscedens et suffodiens--a case report.

Perifolliculitis capitis abscedens et suffodiens is a rare suppurative disease of the scalp of unknown aetiology. The treatment is usually difficult and often disappointing. In the case presented in the current work, the remission was achieved with nine-month isotretinoin treatment.

Identification of melanoma risk factors in the Polish population.

BACKGROUND: There is a great deal of literature regarding malignant melanoma risk factors all over the world. However, such data concerning the Polish population has not been published as of yet. OBJECTIVE: To identify the importance of melanoma risk factors including number and distribution of common and atypical nevi of the patients, phenotypic features, and environmental conditions. METHODS: This is a case-control study of 74 melanoma patients and 300 controls. We used histopathological examination to confirm diagnosis of melanoma. Epiluminescence microscopy was introduced for differential diagnosis of all pigmented lesions. RESULTS: The mean number of common nevi in melanoma patients was significantly higher compared with the control group (22.1 vs 15.2; P < 0.05). Atypical nevi in the melanoma patients group and in the control group were encountered in 16.2% and 6.6%, respectively (P < 0.05). In the melanoma group more patients with fair complexion, intense sun exposure, and sunburn were identified compared with the control group. CONCLUSION: It was stated that an increased number of nevi (especially atypical ones), fair skin, and blue/green eyes, as well as intense UV exposure and sunburns, are important risk factors for melanoma development.

2-chlorodeoxyadenosine (cladribine) induced allergic cutaneous reactions with eosinophilia in a patient with B-cell chronic lymphocytic leukemia.

We present a 68-year old patient with B-cell chronic lymphocytic leukemia (CLL) treated with 2-chlorodeoxyadenosine (2-CdA). This is the first reported patient with B-CLL in whom skin lesions and eosinophilia were observed simultaneously. The most frequent side effect of this drug is myelosuppression with pancytopenia. So far, there have been few reports of cases where either skin reactions or eosinophilia, occurring separately, were observed as side effects from 2-CdA treatment.