Hygienic assessment of protective effects of overalls and individual protective devices used in the production of ampicillin trihydrate and its dosage form, ampicillin sodium salt

The working clothes and individual protective devices recommended by the industrial Rules for the production of ampicillin trihydrate and its medicinal derivatives such as natrium salt ampicillin, do not provide adequate protection of the skin and respiratory mucous from antibiotic contamination. The use of the overalls in combination with the pressurized helmet (designed and produced at the 'Sintez' enterprise) which provided air supply for breathing and, partially, under the overalls, significantly decreased contamination of the body. At the stages of manual handling of the finished products, adequate protection was attained by using the protective paste produced at the 'Altaivitamine' enterprise.     

Prostate thermal therapy with high intensity transurethral ultrasound: the impact of pelvic bone heating on treatment delivery.

PURPOSE: This study was designed to assess pelvic bone temperature during typical treatment regimens of transurethral ultrasound thermal ablation of the prostate to establish guidelines for limiting bone heating. METHODS: Treatment with transurethral planar, curvilinear, and sectored tubular applicators was simulated using an acoustic and biothermal pelvic model that accommodates applicator sweeping, boundary temperature control, and changes in perfusion and attenuation with thermal dose to more accurately model ultrasound energy penetration. The effects of various parameters including power and frequency (5-10 MHz) on bone heating were assessed for a range of prostate cross-sections (3-5 cm) and bone distances (1-3 cm). RESULTS: All devices can produce significant bone heating (temperatures >50 degrees C, thermal dose >240 EM(43 degrees C)) without optimization of applied frequency or power for bone <3 cm from the prostate boundary. In small glands ( approximately 3 cm) increasing operating frequency of curvilinear and planar devices can increase bone temperatures, whereas the tubular applicator can be used at 10 MHz to avoid likely bone damage. In larger prostates (4-5 cm wide) increasing frequency reduces bone heating but can substantially increase treatment time. Lowering power can reduce bone temperature but may increase thermal dose by increasing treatment duration. All applicators can be used to treat glands 4-5 cm with limited bone heating by selecting appropriate power and frequency. CONCLUSIONS: Pubic bone heating during ultrasound thermal therapy of the prostate can be substantial in certain situations. Successful realization of this therapy will require patient-specific treatment planning to optimally determine power and frequency in order to minimize bone heating.     

Magenkarzinom – eine Infektionskrankheit

Gastric cancer still represents the second most common cause of gastrointestinal cancers in Germany. A disturbing issue is that at the time of diagnosis there are less than 15% of patients for whom a cure can be achieved. Nowadays, biological, histomorphological, molecular genetic and epidemiological data suggest that Helicobacter pylori eradication may lead to the prevention of gastric pre-neoplastic lesions and even gastric cancer. At present, eradication can be offered to selected patients and populations at increased risk, but more research is required before embarking on general and global H. pylori eradication for gastric cancer prevention. The main challenge is to determine how long mucosal abnormalities remain reversible and gastric cancer development can be halted.     

Phase I and pharmacokinetic study of gefitinib in children with refractory solid tumors: a Children's Oncology Group Study.

PURPOSE: Epidermal growth factor receptor is expressed in pediatric malignant solid tumors. We conducted a phase I trial of gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, in children with refractory solid tumors. PATIENTS AND METHODS: Gefitinib (150, 300, 400, or 500 mg/m2) was administered orally to cohorts of three to six patients once daily continuously until disease progression or significant toxicity. Pharmacokinetic studies were performed during course one (day 1 through 28). RESULTS: Of the 25 enrolled patients, 19 (median age, 15 years) were fully evaluable for toxicity and received 54 courses. Dose-limiting toxicity was rash in two patients treated with 500 mg/m2 and elevated ALT and AST in one patient treated with 400 mg/m2. The maximum-tolerated dose was 400 mg/m2/d. The most frequent non-dose-limiting toxicities were grade 1 or 2 dry skin, anemia, diarrhea, nausea, and vomiting. One patient with Ewing's sarcoma had a partial response. Disease stabilized for 8 to > or = 60 weeks in two patients with Wilms' tumor and two with brainstem glioma (one exophytic). At 400 mg/m2, the median peak gefitinib plasma concentration was 2.2 microg/mL (range, 1.2 to 3.6 microg/mL) and occurred at a median of 2.3 hours (range, 2.0 to 8.3 hours) after drug administration. The median apparent clearance and median half-life were 14.8 L/h/m2 (range, 3.8 to 24.8 L/h/m2) and 11.7 hours (range, 5.6 to 22.8 hours), respectively. Gefitinib systemic exposures were comparable with those associated with antitumor activity in adults. CONCLUSION: Oral gefitinib is well tolerated in children. Development of the drug in combination with cytotoxic chemotherapy will be pursued.     

Voltammetric Quality Control of Bioactive Additives: Determination of B<Subscript>1</Subscript>, B<Subscript>2</Subscript>, C,E Vitamins and Quercetin

Rapid voltammetric procedures for the determination of water-soluble vitamins C, B₁, and B₂, fat-soluble vitamin E (α-tocopherol acetate), and quercetin in bioactive food additives have been developed. The systematic error (i.e., correctness) of the proposed procedures was evaluated using certified reference materials and the additive recovery tests, which gave the following limiting metrological characteristics: relative error, 25 %; reproducibility, 28 %; convergence, 22 %. The full analysis time (with sample preparation) did not exceed 2 hours. Voltammetric determinations under optimum conditions can be performed in the automated regime controlled by a computer according to the specially developed software.__________Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 39, No. 3, pp. 54 – 56, March, 2005.     

Alkaline Hydrolysis Kinetics and No-Donor Activity of Tenonitrozole

The kinetics of alkaline hydrolysis of N-(5-nitro-2-thiazolyl)-2-thiophenylcarboxamide (tenonitrozole or atrican) has been studied by photometric and polarographic techniques, and the thermodynamic parameters in the intermediate state of this process were determined. A mechanism explaining the nitric oxide (NO) production during the hydrolytic decomposition of tenonitrozole is proposed. It is suggested that the antiprotozoal and antimicrobial activity of this drug under anaerobic conditions is related to the formation of nitro radical anions and NO. Under aerobic and microaerophilic conditions, the hydrolysis of tenonitrozole may lead to the formation of a peroxynitrite anion, which is a strong cytotoxic agent. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 39, No. 6, pp. 15 – 18, June, 2005.     

Toll-like receptor signaling inhibits structural development of the distal fetal mouse lung.

We tested the hypothesis that innate immune signaling in utero could disrupt the structural development of the fetal lung, contributing to the pathogenesis of bronchopulmonary dysplasia. Injection of Escherichia coli lipopolysaccharide (LPS) into the amniotic fluid of E15 BALB/cJ mice increased the luminal volume density of fetal mouse lungs at embryonic day (E) 17 and E18. LPS also increased luminal volume and decreased distal lung branching in fetal mouse lung explants. This effect required NF-kappaB activation and functional Toll-Like Receptor 4. Airway branching may require fibronectin-dependent epithelial-mesenchymal interactions, representing a potential target for innate immune signaling. Anti-fibronectin antibodies and LPS both blocked distal lung branching. By immunofluorescence, fibronectin localized to the clefts between newly formed airways but was restricted to peripheral mesenchymal cells in LPS-exposed explants. These data suggest that LPS may alter the expression pattern of mesenchymal fibronectin, potentially disrupting epithelial-mesenchymal interactions and inhibiting distal airway branching and alveolarization. This mechanism may link innate immune signaling with defects in structural development of the fetal lung.