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

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

Preformulation development of recombinant pegylated staphylokinase SY161 using statistical design

The goal of this study was to perform preformulation development of SY161 by using statistical design methods to understand the effects of buffer strength, NaCl concentration, and pH on conformation and stability of the protein. It was also important to elucidate interactions between these factors. A central composite design using a 2-level full-factorial study was performed. Secondary structure was evaluated using circular dichroism. Stability toward unfolding was investigated using high-sensitivity differential scanning calorimetry. Depegylation, aggregation, and protein loss were evaluated using SEC-HPLC with on-line light scattering, at time zero and after a 2-week stability study. Response surface plots clearly show optimal pH, NaCl, and buffer conditions. Interactions between pH and NaCl as well as pH and buffer concentration are observed. Tm is seen to be predictive of SY161 stability. Secondary structure changes were minimal and did not influence stability. Statistical design was very effective in providing an understanding of the effects of the formulation components on SY161 stability