In vitro pharmacology of inosine, with special reference to possible interactions with capsaicin-sensitive mechanisms and inflammatory mediators.

The in vitro pharmacology of inosine (Ino), a putative anti-inflammatory compound, has been investigated in smooth muscle preparations, with emphasis on its possible interaction with known inflammatory mediators, as well as capsaicin, an inducer of "neurogenic inflammation". The highest concentration of Ino routinely studied was 1 mM, since 10 mM nonspecifically inhibited many types of smooth muscle motor responses. In the guinea pig isolated ileum or trachea, Ino (1 mM) failed to influence the excitatory effect of capsaicin. The nitric oxide (NO)-mediated relaxant effect of capsaicin in the human colonic circular muscle was not influenced by Ino. Ino only weakly reduced the contractile effect of histamine on the guinea pig ileum. Substance P-mediated nonadrenergic, noncholinergic (NANC) contractions evoked by electrical stimulation in the guinea pig ileum were inhibited by half by Ino (1 mM). Ino showed no or only a weak inhibitory effect on NANC relaxation of the rat ileum. Arachidonic acid- or leukotriene D(4)-induced contractions of the guinea pig ileum were only moderately inhibited by Ino. Collectively, these results indicate that Ino (up to 1 mM) shows no major antagonist activity at histamine H(1) receptors, leukotriene CysLT(1) receptors, the transient receptor potential channel TRPV1 or tachykinin NK(1) or NK(2) receptors, or cyclooxygenase-inhibitory activity. Therefore, its anti-inflammatory activity is probably not associated with these mechanisms. The in vitro methods used in this study are capable of detecting a wide range of biological effects and hence may be recommended as a screening procedure for potential drugs or natural products.

P2 purinoceptor antagonists inhibit the non-adrenergic, non-cholinergic relaxation of the human colon in vitro.

Neurotransmitters released by myenteric neurons regulate movements of intestinal smooth muscles. There has been little pharmacological evidence for a role of purinergic mechanisms in the non-adrenergic, non-cholinergic (NANC) relaxation of the human large intestine. We used P(2) purinoceptor antagonists to assess whether such receptors are involved in the NANC relaxation of the circular muscle of the human sigmoid colon. It was also investigated whether the guanylate cyclase enzyme mediates the NANC response. Human colonic circular strips were tested in organ bath experiments with isotonic recording. NANC, non-nitrergic relaxations induced by electrical field stimulation (1 and 10 Hz, in the presence of atropine, guanethidine, and 100 microM N(G)-nitro-L-arginine [L-NOARG]) were strongly inhibited by a combination of the P(2) purinoceptor antagonists pyridoxal-phosphate-6-azophenyl-2',4'-sulfonic acid (PPADS) (50 microM) and suramin (100 microM). PPADS plus suramin was ineffective in the absence of L-NOARG. L-NOARG alone significantly reduced the NANC relaxation to electrical stimulation. PPADS plus suramin strongly inhibited the relaxation in response to exogenous alpha,beta-methylene ATP. The guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (3 microM) inhibited the NANC relaxation, but did not add to its reduction by L-NOARG. L-NOARG was still slightly effective in the presence of ODQ. Vasoactive intestinal polypeptide tachyphylaxis failed to influence the non-nitrergic NANC relaxation. It is concluded that nitric oxide (NO) and ATP co-mediate, in a non-additive manner, the NANC relaxation. NO probably acts through the guanylate cyclase, though a small fraction of its effect might be mediated by other mechanisms. Activators of the guanylate cyclase other than NO do not seem to participate in the NANC relaxation.

Transvaginal extraction of the laparoscopically removed spleen.

Laparoscopic removal of normal and moderately enlarged spleens has become the gold standard operation in recent years because its short operative time, technical safety, and quick patient recovery time. The best method for extraction of the removed spleen, however, has not yet been determined. The authors present a new method for the extraction of the laparoscopically removed spleen. Using a transvaginal approach, the organ is removed through an incision on the posterior vaginal wall and exteriorized in a laparobag. The procedure is similar to a routine vaginal hysterectomy, but is technically much simpler to perform.

Nitric oxide is involved in the relaxant effect of capsaicin in the human sigmoid colon circular muscle.

The relaxant effect of capsaicin (300 nM) has been studied on mucosa-free circular strips of the human sigmoid colon in vitro. The response of precontracted preparations to capsaicin (sub-maximal relaxation) was reduced by over 50% by the nitric oxide synthase inhibitor N(G)-nitro- L-arginine (L-NOARG; 20 microM or 100 microM) or by the guanylate cyclase inhibitor 1 H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 1 microM), but not by tetrodotoxin (1 microM) or the P(2) purinoceptor antagonist pyridoxal phosphate 6-azophenyl-2',4'-disulfonic acid (PPADS; 50 microM). L-NOARG or ODQ caused moderate contraction of the circular muscle, indicating a tonic "nitrergic" control. Anandamide (1-100 microM), an endogenous cannabinoid and capsaicin VR(1) receptor stimulant, failed to either mimic or modify the response to capsaicin (300 nM). It is proposed that capsaicin causes the release of smooth muscle relaxant substance(s) from afferent nerve endings in the gut wall, in a tetrodotoxin-resistant manner. Nitric oxide (possibly released from capsaicin-sensitive afferents) plays an important role in the capsaicin-evoked response. No evidence has been found for an involvement of PPADS-sensitive P(2) purinoceptors in the response to capsaicin or for a stimulation or inhibition of capsaicin-sensitive receptors by anandamide in the human sigmoid colon.

The hourglass appearance of the neurofibroma on rectal ultrasound. A case report.

Colorectal manifestation of von Recklinghausen's disease is a rare entity. The typical dumbbell shape of the lesion has been described previously, but only from a resected cecal specimen. The authors present the endosonographic appearance of a rectal neurofibroma, which shows a similar hourglass shape, thus facilitating the diagnosis.

[Current treatment of anal fissure]. / Az analis fissura modern kezeléséról.

More and more authors believe, that the cause of the chronic anal fissure is the increased anal resting pressure. It maintains a vicious circle causing ischaemia and ulcer on the anoderm. There are many traditional surgical methods treating fissures apart from the conservative ways. However, these are likely to cause significant morbidity. Chemical sphincterotomy seems to be a novel way and its most effective drugs are the nitrates. 75-80% of the patients can be cured with the topical use of these. This treatment has to be accompanied with the normalisation of the stools. If the symptoms persist after 6-8 weeks the procedure of choice is the lateral sphincterotomy. Authors evaluate the different treatments based on a literature overview and own experiences. They also suggest a treatment protocol.

Local recurrence of rectal cancer following preoperative irradiation.

The authors investigated local recurrence of rectal cancer in patients' groups preoperatively irradiated (40-50 Gy) or treated by surgery alone. In advanced disease both treatment groups were administered postoperative chemotherapy, too. Local recurrence was observed in 30.2% in patients treated by surgery alone, while it dropped to 11.65% in the patients' group subjected to radiation therapy prior to surgery (p < 0.05). Impairment of degree of differentiation resulted in an enhanced number of recurrences in both groups, even if they appeared later in irradiated patients.

Ftorafur therapy in acute pancreatitis.

The authors tested Ftorafur (N1-2'-furanidyl-5-fluorouracyl) in patients with acute pancreatitis on the basis of experimental and clinical data. The daily dosage was 200 mg (3-4 mg/kg body weight). In the course of treatment the serum and urine levels of amylase and the changes in WBC were studied. The results were compared to that obtained in patients with acute pancreatitis but were not given Ftorafur. Urine amylase levels decreased significantly in response to Ftorafur treatment over three days. The decrease of serum amylase levels and WBC was not significant in either group. The advantages of Ftorafur treatment are as follows: levels of amylase in serum and urine are normalized earlier, the duration of treatment, hence costs are decreased, Ftorafur produced a cytoprotective effect due to the inhibition of protein synthesis in the pancreas.

The effect of 5-fluorouracil on experimental acute pancreatitis.

The present study was undertaken to elucidate the effects of different doses of 5-fluorouracil on experimental acute pancreatitis. Twelve mongrel dogs were used. Acute pancreatitis was induced by intraductal injection of sunflower-oil. Two groups of animals were treated with intravenous 5-fluorouracil: 1 mg/kg body weight for the first group of 5 animals, and 5 mg/kg body weight for the second one of 7 animals in subsequent three postoperative days. All the animals in the first group died within 24 to 36 hours due to acute haemorrhagic pancreatitis. All the animals in the second one survived longer than 36 hours. A statistically significant increase of serum amylase and lipase levels was found in pancreatitis with significant decrease of them during treatment. Three to 8 weeks later signs of chronic pancreatitis could be detected in surviving dogs.

Passage through the lymph node. II. Functional dependence on the site of application of antigens.

Following a previous comment on the compartmentalization of lymph nodes by lymphography performed through separate bundles of afferent lymphatics, the authors attempted to prove that sectoral arrangement has its functional equivalent, too. They found an elective uptake of tritiated thymidine and a rather circumscript response in cellular activity, if antigenic stimuli--such as VX-2 carcinoma cells and living BCG colonies--were transferred through the same bundle of afferent lymphatics which supply the lymph node part investigated.

Histological and autoradiographic changes in locally irradiated lymph nodes (an experimental study on rabbits).

The authors studied the local effect of 3000 Rxl X-ray irradiation on the popliteal lymph nodes of rabbits. Beside the morpho-histological description autoradiography was performed after injection of H3-thymidine in the afferent lymphatic of the irradiated knee node. The main finding is the appearance of newly-formed germinal centers between the 6-10. days after irradiation.

Passage through the lymph node. Studies with watered and oiled contrast medium given into an afferent lymphatic.

The authors investigated the passage of watered and oiled contrast media through the lymph node. Patent Blue dye diluted in saline has delineated as a rule only a circumscript area of the lymph node according to the supplying area of the afferent cannulated. Lipiodol Ultrafluid has been found suitable for filling up the whole node: at first only a small part of the node became filled primarily from the afferent, while other parts were filled secondarily from the hilus. The compartmentalisation of the lymph node has been proved by autoradiography (3H-thymidine), too.