Synthesis and antitumor activity of hydrosoluble analogs of p-(3,3-dimethyl-1-triazeno) benzoic acid potassium salt

he hydrosoluble triazene derivatives of phenylacetic, phenylbutyric and cinnamic acid have been synthesized and their logP and pKa values were simultaneously determined according to a multiparametric fitting of potentiometric data. The antitumor activity caused by the synthesized compounds in mice bearing either Lewis lung carcinoma or TLX5 lymphoma was evaluated and discussed in comparison with the parent compound (p-(3,3-dimethyl- 1-triazeno)benzoic acid potassium salt (DM-COOK, CAS 70055-49-1). The tested compounds were at least as active as DM-COOK, the cinnamic and the phenylacetic derivatives being the more active compounds in mice bearing TLX5 lymphoma and Lewis lung carcinoma, respectively

Arginase Immobilization on Poly(hydroxyethyl acrylate) Matrix Beads

A study was made on the preparation and behaviour of polymer matrix im mobilized arginase, an enzyme involved in the urea cycle. Immobilization of purified calf liver arginase was obtained by a physical entrapment method based on the low temperature polymerization induced by radiation of a glass forming monomer mixed with an aqueous solution of the enzyme. Enzymatic activity was found to be retained in an acceptable range (30-35%) in a bead shaped matrix only when the monomer was hydroxyethylacrylate (HEA) purified by alkaline extraction and a particular sample preparation procedure was followed. The poly(hydroxyethyl acrylate) (PHEA) immobilized arginase was characterized by evaluating its chemical and enzymological properties such as Km, activation energy, stability to proteolytic enzymes, and activity de pendence on pH. Performance runs of continuous biocatalytic conversion of ar ginine to ornithine were carried out utilizing a reactor consisting of a column with immobilized arginase beads. After weeks of operation the substrate con version remained almost constant, indicating a practically unaltered enzy matic activity. PHEA immobilized arginase beads also retained their activity for days either in the presence of whole blood or when implanted intraperi toneally or subcutaneously into rats. No significant inflammation or other adverse reactions were observed after one week of residence of such implants. This seems promising for lowering the arginine blood level in specific diseases

Antimetastatic action and lymphocyte activation by the modified lysozyme mPEG-Lyso in mice with MCa mammary carcinoma

The effects of Lysozyme (hen egg-white lysozyme) and of its modified derivative mPEG-Lyso, (Lysozyme coupled with monomethoxypolyethylenglycol) were tested on CBA mice bearing MCa mammary carcinoma. mPEG-Lyso, given by the oral route at a dose comparable to 100 mg/kg/day of native Lysozyme, is at least as active as Lysozyme for the activation of lymphocytes obtained from different districts along the axis GALT-spleen. These effects were evidenced by measuring the in vitro response of lymphocytes of animals treated in vivo with ConA and LPS using the SRB test, and measuring the content of nucleic acids by cytofluorimetric analysis. Lymphocytes obtained from the mesenteric lymph nodes of animals treated with mPEG-Lyso, show a response to ConA and to LPS at early stages of treatment, when tumor growth reduces the response to controls. mPEG-Lyso, was also effective on lung metastasis formation. Considering that mPEG-Lyso,, compared to the native Lysozyme, completely lost its enzymatic action on Micrococcus lysodehycticus cell walls, this data suggest that the effects of lysozyme on immunity and on tumour growth are unrelated to the production of immunoactive peptidoglycans in the gut

One-year follow-up after laparoscopic Heller-Dor operation for esophageal achalasia

Background: The Heller-Dor operation has recently been proposed for the treatment of esophageal achalasia even via a laparoscopic approach. Methods: To measure the medium-term effectiveness of this new minimally invasive technique, an evaluation of preand postoperative symptoms, esophagogram, endoscopic findings, esophageal manometry, and pH monitoring was prospectively designed in 43 patients with primary esophageal achalasia. The mean clinical follow-up for all the patients is 12 months (range 3-43), while the mean radiological follow-up is 11 months (range 1-23). Endoscopic data 1 year after surgery are currently available for 27 patients (63%), whereas a 12-month (range 1-26) functional followup (including manometric and pH-monitoring studies of the esophagus) is currently available for 35 patients (81.4%). Results: No dysphagia was reported in 38 cases (88.4%); two (4.6%) complained of occasional swallowing discomfort which regressed spontaneously; two (4.6%) had persistent dysphagia which regressed with pneumatic dilatation. One patient (2.8%) reported mild occasional dysphagia after a 1-year asymptomatic period. Preoperatively, esophagograms showed an average maximum diameter of 40.6 \ub1 9.1 mm which decreased to 24.1 \ub1 6.0 mm after operation. Mean lower esophageal sphincter (LES) resting and residual pressures decreased significantly from 28.6 \ub1 10.7 mmHg to 8.8 \ub1 4.1 mmHg and from 17.0 \ub1 9.7 mmHg to 4.7 \ub1 4.0 mmHg, respectively (p < 0.0001). These effects on esophageal diameter and LES function seem to persist over time. The complete absence of any peristaltic contractions recorded preoperatively in all cases remained unchanged after surgery in all but four patients. However, this rare recovery of peristalsis proved to be transient, and patients revealed a manometric impairment of their esophageal body function, but without complaining of dysphagia. Twenty-four-hour pH monitoring showed abnormal gastroesophageal reflux episodes in two (5.7%) of the 35 patients who were monitored: one was asymptomatic; the other had heartburn and endoscopically demonstrated grade II esophagitis. Conclusions: Laparoscopic Heller-Dor operation achieves excellent medium-term results which, together with the already-demonstrated advantages of a minimal surgical trauma and rapid convalescence, validate the use of such a minimally invasive approach to treat patients with primary achalasia of the esophagus