Effects of capsaicin,tachykinins, calcitonin gene-related peptide and bradykinin in the pig iris sphincter muscle

Summary Capsaicin-sensitive sensory neurons of the rabbit iris, by releasing tachykinins, exert a major role in the control of pupil motility in response to various noxious stimuli. However, the contribution of sensory innervation to the regulation of iris smooth muscle tone in other mammals species is not known. We have studied the effects produced by electrical field stimulation, capsaicin, substance P, neurokinin A, calcitonin gene-related peptide (CGRP), and bradykinin in the isolated iris sphincter muscle of the pig.Capsaicin (10 M): a) contracted the isolated sphincter muscle and; b) released immunoreactivity for substance P (SP-LI) and CGRP (CGRP-LI) from this preparation. These two effects were no longer observed at the second exposure to the drug. Electrical field stimulation (10 Hz, 60 V, 0.5 ms for 5 s) produced a biphasic contractile response. The rapid component was inhibited by atropine (1 M), while the delayed response was blocked by previous exposure to capsaicin (10 M).Substance P and neurokinin A consistently produced contraction of the pig iris sphincter muscle, substance P being more potent than neurokinin A. CGRP induced a contractile response in more than 50% of the preparations. The tachykinin antagonist [D-Argl, D-Trp^7,9, Leu¹¹-substance P (3 M) blocked: a) the effect of substance P (1 nM); b) the delayed response to electrical field stimulation and; c) reduced by more than 50% response to capsaicin. Bradykinin (10 M) failed to release either SP-LI or CGRP-LI. The contractile response evoked by bradykinin was unaffected by in vitro pretreatment with capsaicin (10 M).The existence in the pig iris of capsaicin-sensitive sensory fibres releasing neuropeptides and thus regulating sphincter muscle tone is proposed. Send offprint requests to Dr. P. Geppetti at the above address     

Capsaicin-like activity of some natural pungent substances on peripheral endings of visceral primary afferents

Summary 1. The effects of some naturally occurring pungent substances, piperine, mustard oil, eugenol and curcumin, were compared to those of capsaicin in the rat isolated urinary bladder. 2. All test compounds dose-dependently contracted the rat bladder and produced desensitization toward capsaicin (1 mol/l). Development of cross-tachyphylaxis among the natural pungent substances on one hand and capsaicin on the other, suggested a common site of action on visceral primary afferents. 3. Contractile responses to piperine, mustard oil and eugenol were partially tetrodotoxin and ruthenium red-sensitive, suggesting that activation of sensory terminals by these agents takes place indirectly, as well as by a direct action on sensory receptors. 4. The presence of the secondary acylamide linkage (present in the backbone of capsaicin, but not in that of test compounds) does not appear to be essential to produce desensitization of sensory nerve terminals. Send offprint requests to R. Patacchini at the above address     

Does the level of stapled ileoanal anastomosis influence physiologic and functional outcome?

PURPOSE: The aim of this investigation was to ascertain how the length of anal canal preserved above the dentate line in stapled end-to-end ileoanal anastomosis influenced late outcome. METHODS: Two groups, high cuff group and low cuff group of nine subjects with stapled anastomosis, matched for sex, age, pouch configuration, and mean follow-up, representing the highest (median, 2.5 cm) and lowest (median, 0.7 cm) anal cuff lengths in our series, were selected. Physiologic and functional parameters were appraised preoperatively, at the time of ileostomy closure, and at 1, 3, 6, and 12 months after reestablishment of intestinal continuity. RESULTS: At one year, the drop in mean anal canal resting pressure was 13 percent in the high cuff group (not signficant) and 31 percent in the low cuff group (P <0.05); mean maximum squeezing pressure did not differ significantly from preoperative values in both groups. The mean volume of the ileal pouch was higher in the low cuff group at all insufflation pressures. The rectoanal inhibition reflex reappeared in four high cuff group patients and in none of the low cuff group patients. Mean distention pressure (cm H ₂ O) and volume (ml) eliciting urge sensation were 80 and 360 in the low cuff group compared with 40 and 240 in the high cuff group (P ?0.05). Daytime bowel movements and night incontinence were significantly better in the low cuff group. No statistical differences were observed for night stool frequency, daytime incontinence, pad use (day and night), discrimination between gas and feces, ability to defer evacuation, and difficulty in emptying the pouch. CONCLUSION: Patients with stapled anastomoses and a low rectal cuff length, despite presenting lower anal resting pressure and absence of rectoanal inhibition reflex, had a better functional outcome in terms of continence than those with a high cuff length.     

Radiosurgery in the treatment of the glottic plane carcinoma

During the last 20 years, various conservative surgical techniques have been proposed to treat larynx cancer. On the basis of our various experiences and of the ultrastructural data on the tissues treated with radiowaves, we decided to also use radiosurgery in operations under direct microlaryngoscopy. We select 18 patients suffering from epidermoid carcinoma. These patients had been referred to our ENT clinic at the Polichnico of Palermo between 1999 and 2001. The authors describe the surgical procedures used and emphasize the advantages of radiosurgery in the treatment of larynx cancer.     

In Vitro Effects of Retinoids on the Proliferation and Differentiation Features of Epstein-Barr Virus-Immortalized B Lymphocytes

Retinoids have been shown to be effective in the chemoprevention and treatment of certain human malignancies. In this review, we will summarize our recent results concerning the effects of retinoids on the proliferation and differentiation of Epstein-Barr virus (EBV)-immortalized lymphoblastoid B-cell lines (LCLs), an in vitro model of EBV-related lymphoproliferative disorders arising in immunosuppressed hosts. Retinoids proved to be powerful inhibitors of the proliferation of EBV-infected LCLs in vitro, with 13-cis-retinoic acid (RA), all-trans-RA, and 9-cis-RA being the most effective compounds. Of note, retinoid-induced growth arrest in vitro appears irreversible at drug concentrations (10-^-6 mol/L) which may be reached in man after oral systemic therapy. The antiproliferative activity exerted by retinoids on LCLs is a generalized phenomenon usually associated with a progressive accumulation in G₀/G₁ phases of treated cells. The strong upregulation of p27^Kipl invariably observed in cells exposed to retinoids may contribute to the decreased number of cycling cells, probably by inhibiting the transition from the G₁ to S phase. Moreover, we obtained evidence indicating that the antiproliferative effects of retinoids are not dependent on the induction of terminal differentiation of EBV-immortalized B lymphocytes. In fact, the modifications induced by retinoids relative to LCL morphology, phenotype (downregulation of CD19, HLA-DR, and s-Ig, and upregulation of CD38 and c-Ig), and IgM production were highly variable among the lines tested and often only slightly relevant. Finally, the antiproliferative activity exerted by retinoids on LCLs is not mediated by a direct modulation of viral latent antigens, since EBNA-2 and LMP-1 downregulation was a late event detected only in some cell lines. These results indicate that retinoids may be useful in the medical treatment of EBV-related lymphoproliferative disorders of immunosuppressed patients, particularly in the earlier phases of these diseases.     

Advanced colorectal cancer in the elderly: results of consecutive trials with 5-fluorouracil-based chemotherapy

To evaluate toxicity and efficacy of chemotherapy in elderly patients (≥65 years of age) with advanced colorectal cancer, data from two consecutive trials conducted between 1984 and 1995 at the National Institute for Cancer Research were analysed comparing the results of treatment in those 65 years of age or older and in those younger than 65 years. Of 215 patients recruited, 82 elderly patients (median age 70 years, median performance status 1) received one of the following regimens based on 5-fluorouracil (5-FU): (1) weekly 5-FU 600 mg/m² i.v. bolus (30 patients); (2) weekly 5-FU 600 mg/m² bolus plus leucovorin (LV) 500 mg/m² 2-h i.v. infusion (28 patients); (3) Weekly 5-FU 2600 mg/m² 24-h continuous i.v. infusion plus LV 100 mg 4-h i.v. infusion and 50 mg orally every 4 h for five doses (24 patients). Overall, 1071 chemotherapy cycles were administered with a median number of 12 courses per patient. The main side effects were diarrhoea, observed in 38% of patients, stomatitis in 24% of patients and hand-foot syndrome in 13% of patients, and haematological toxicity affected only 15% of patients. No patient suffered grade IV toxicity. In three patients chemotherapy was discontinued because of toxicity (two patients suffered grade III diarrhoea, one patient grade III hand-foot syndrome). No significant difference in toxicity was evident between patients older than or younger than 65 years. Analysis of median dose intensity demonstrated no difference between the two groups. Overall objective response was observed in 18% (95% confidence limits 11–29) of elderly patients (15/82) in comparison with 23% (95% CL 17–32) of patients <65 years of age (31/133 pts). In conclusion, chemotherapy in elderly patients with advanced colorectal cancer is a safe and effective treatment with acceptable toxicity and comparable objective response rates. Received: 6 January 1998 / Accepted: 27 February 1998     

Polyvinylchloride infusion lines expose infants to large amounts of toxic plasticizers

PURPOSE: The purpose of this study was to evaluate whether infusion lines are able to leach plasticizers in substantial amounts and thus be a candidate substance for hepatotoxic effects during long-term total parenteral nutrition (TPN). METHODS: TPN solutions, blood products, and selected drugs typical for preterm infants concerning amount, content, and infusion time were perfused through common polyvinylchloride (PVC) infusion lines. Concentration of diethylhexyl-phthalate (DEHP) before and after perfusion was determined by gas chromatography/mass spectrometry. RESULTS: Daily quantities of DEHP by 24-hour infusions were Lipid emulsion 20%: 10185.6 microg; aminoacid/glucose-solution: 116.2 microg; midazolaminfusion for sedation: 26.4 microg; fentanyl for sedation: 132.5 microg; propofol for sedation: 6561.0 microg. The amount of DEHP by single doses of blood products (20 mL) were packed red blood cells: 144-608 microg; platelet rich plasma: 928 microg; and fresh frozen plasma: 552-8108 microg. The dose of DEHP for a typical preterm neonate requiring TPN and additional therapy like sedation or blood products is at minimum 10 mg and can easily reach 20 mg/d. CONCLUSION: This large amount of DEHP is especially disturbing, because it effects the most vulnerable patients (neonates). Whether there is a relation to TPN-induced hepatobiliary dysfunction remains to be elucidated and is under investigation. With respect to recent literature, a biological effect of these doses must be assumed.