Inhibition of cyclooxygenase-2 indirectly potentiates antitumor effects of photodynamic therapy in mice.

PURPOSE: The aim of the present study was to potentiate the antitumor effectiveness of photodynamic therapy (PDT). A cDNA microarray analysis was used to evaluate the gene expression pattern after Photofrin-mediated PDT to find more effective combination treatment with PDT and inhibitor(s) of the identified gene product(s) overexpressed in tumor cells. EXPERIMENTAL DESIGN: Atlas Mouse Stress Array was used to compare the expression profile of control and PDT-treated C-26 cells. The microarray results have been confirmed using Western blotting. Cytostatic/cytotoxic in vitro assay as well as in vivo tumor models were used to investigate the antitumor effectiveness of PDT in combination with cyclooxygenase (COX) 2 inhibitors. RESULTS: PDT induced the expression of 5 of 140 stress-related genes. One of these genes encodes for COX-2, an enzyme important in the tumor progression. Inhibition of COX-2 in vitro with NS-398, rofecoxib, or nimesulide, or before PDT with nimesulide did not influence the therapeutic efficacy of the treatment. Administration of a selective COX-2 inhibitor after PDT produced potentiated antitumor effects leading to complete responses in the majority of treated animals. CONCLUSIONS: COX-2 inhibitors do not sensitize tumor cells to PDT-mediated killing. However, these drugs can be used to potentiate the antitumor effectiveness of this treatment regimen when administered after tumor illumination.     

Usefulness of high doses of glucocorticoids and hyperbaric oxygen therapy in sudden sensorineural hearing loss treatment.

OBJECTIVE: We investigated the effect of pharmacologic (steroids, vasodilators, vitamins, and Betaserc) and hyperbaric oxygen therapy on patients with sudden sensorineural hearing loss. METHODS: The pharmacologic arm of the study consisted of 52 patients with defined sudden sensorineural hearing loss treated simultaneously in the ENT Department and National Center for Hyperbaric Medicine of the Medical University of Gdansk, Poland, from 1997 to 2000 (Group A). The hyperbaric oxygen therapy consisted of exposure to 100% oxygen at a pressure of 250 kPa for a total of 60 minutes in a multiplace hyperbaric chamber. The control group included 81 patients with defined sudden sensorineural hearing loss treated in the ENT Department, Medical University of Gdansk, from 1980 to 1996 (Group B). Both groups were comparable regarding the age of the patients, season of hearing loss occurrence, tinnitus and vestibular symptom frequency, delay before therapy, and average threshold loss before the start of treatment. The treatment results (hearing gain) were estimated using pure-tone audiometry. We retrospectively analyzed the audiograms of all patients. RESULTS: Patients from Group A (blood flow-promoting drugs, glucocorticoids in high doses, betahistine, and hyperbaric oxygen therapy) showed significantly better recovery of hearing levels compared with those from Group B (blood flow-promoting drugs and glucocorticoids in low doses) at seven frequencies (500, 1,000, 2,000, 3,000, 4,000, 6,000, and 8,000 Hz) (p < 0.05) and four groups of frequencies (pure-tone average, high-tone average, pure middle-tone average, and overall average) (p < 0.05). Percentage hearing gain in all investigated frequencies was also better in Group A versus Group B, and the differences were statistically significant (p < 0.05). CONCLUSION: We conclude that hyperbaric oxygen therapy with high doses of glucocorticoids improves the results of conventional sudden sensorineural hearing loss treatment and should be recommended. In addition, the best results are achieved if the treatment is started as early as possible.     

Sexual Functioning in Female Patients Undergoing Surgical Treatment for Colorectal Cancer—A Single-Center,Prospective Triple Timepoint Yearly Follow-Up

The study was aimed at assessing the quality of sexual functioning in female patients having undergone surgical treatment for cancer depending on the type of surgery. The prospective cohort consisted of 48 female patients (23 patients with stoma [A2] and 25 patients with maintained continuity of the GI tract [A1]). Study methods included a diagnostic survey and the analysis of medical records of patients. Research tools consisted of a standardized FSFI questionnaire and a proprietary form for evaluation of sociodemographic data. Measurements were performed at threetimepoints: On the day before the surgery (Measurement I) as well as six and 12 months after the surgery (Measurements II and III, respectively). Statistically significant differences in results were observed in Measurements II and III in the subscales of arousal (II:p = 0.0068, III:p = 0.0018), lubrication (II:p = 0.0221, III:p = 0.0134), orgasm (II:p = 0.0044, III:p = 0.0021), satisfaction (II:p = 0.0021, III:p = 0.0433), and pain/discomfort (II:p = 0.0343, III:p = 0.0473). In all cases, lower scores corresponding to lower quality of sexual functioning were observed in patients in whom stoma had been performed. Statistically significant differences in sexual functioning were observed at Measurements II and III in each group, with the results being significantly (p > 0.05) worse in patients having undergone Hartmann’s procedure or abdominoperineal resection). Variables significantly affecting self-assessed sexual satisfaction included marital status, age, and modality of neoadjuvant treatment. Restoration of the continuity of the gastrointestinal tract is a chance for better self-assessment of the patient’s quality of life as regards sexual functioning.     

Photogrammetry-Based Volume Measurement Framework for the Particle Density Estimation of LECA

This paper presents a photogrammetry-based volume measurement framework for the particle density estimation of Lightweight expanded clay aggregate (LECA). The results are compared with computed tomography (CT) and Archimedes’ method measurements. All of the steps required in order to apply the proposed approach are explained. Next, we discuss how the interpretation of open pores affects the results of volume measurements. We propose to process the shapes obtained from different methods by applying an Ambient Occlusion algorithm with the same threshold, t = 0.175. The difference between the CT and SfM methods is less than 0.006 g/cm³, proving that the photogrammetry-based approach is accurate enough. The Archimedes’ method significantly overestimates the density of the particles. Nevertheless, its accuracy is acceptable for most engineering purposes. Additionally, we evaluate the accuracy of shape reconstruction (in terms of the Hausdorff distance). For 95% of the grain’s surface, the maximum error is between 0.073 mm and 0.129 mm (depending on the grain shape). The presented approach is helpful for measuring the particle density of porous aggregates. The proposed methodology can be utilized in order to estimate intergranular porosity, which is valuable information for the calibration of DEM models.     

Oxazoline scaffold in synthesis of benzosiloxaboroles and related ring-expanded heterocycles: diverse reactivity,structural peculiarities and antimicrobial activity

Two isomeric benzosiloxaborole derivatives 3a and 5a bearing fluorine and 4,4-dimethyl-2-oxazolin-2-yl substituents attached to the aromatic rings were obtained. Both compounds were prone to hydrolytic cleavage of the oxazoline ring after initial protonation or methylation of the nitrogen atom. The derivative 3c featuring N-methylammoniumalkyl ester functionality was successfully subjected to N-sulfonylation and N-acylation reactions to give respective derivatives which demonstrates its potential for modular synthesis of structurally extended benzosiloxaboroles. Compound 5c bearing N-ammoniumalkyl ester underwent conversion to a unique macrocyclic dimer due to siloxaborole ring opening. Furthermore, an unexpected 4-electron reduction of the oxazoline ring occurred during an attempted synthesis of 5a. The reaction gave rise to an unprecedented 7-membered heterocyclic system 4a comprising a relatively stable B–O–B–O–Si linkage and stabilized by an intramolecular N–B coordination. It could be cleaved to derivative 4c bearing BOH and SiMe₂OH groups which acts as a pseudo-diol as demonstrated by formation of an adduct with Tavaborole. Apart from the multinuclear NMR spectroscopy characterization, crystal structures of the obtained products were determined in many cases by X-ray diffraction. Investigation of biological activity of the obtained compounds revealed that derivatives 3e and 3f with pendant N-methyl arylsulfonamide groups exhibit high activity against Gram-positive cocci such as methicillin-sensitive Staphylococcus aureus ATCC 6538P, methicillin-resistant S. aureus (MRSA) ATCC 43300 as well as the MRSA clinical strains, with MIC values in the range of 3.12–6.25 mg L⁻¹. These two compounds also showed activity against Enterococcus faecalis ATCC 29212 and Enterococcus faecium ATCC 6057 (with MICs of 25–50 mg L⁻¹). The results of the antimicrobial activity and cytotoxicity studies indicate that 3e and 3f can be considered as potential antibacterial agents, especially against S. aureus MRSA.

Transformations of oxazoline–benzosiloxaborole conjugates gave rise to novel boracyclic systems as well as functionalized derivatives featuring antibacterial activity.     

Rho kinase--a new target for pharmacological treatment of an overactive bladder

Rho kinase plays a key role in the regulation of smooth muscles contraction, including those of the urinary bladder detrusor. Rho kinase pathway modulates the level of phosphorylation of the myosin light chain, mainly through the inhibition of myosin phosphatase. Recent experimental data indicate that its role might be exacerbated in local and systemic pathological conditions which affect the bladder. It seems that Rho kinase inhibitors, such as Y27632, may turn out to be an effective group of drugs in pharmacotheraphy of an overactive bladder (OAB), which will influence the storage phase of the micturition cycle, without interfering with the physiological voiding.     

Pathogenesis and genetics of neural tube defects

After congenital heart defects neural tube defects (NTDs) is the second most prevalent congenital malformation among birth defects. The average rate of isolated NTDs is 1.4-2.0 per 1000 live births worldwide. The etiology of isolated (nonsyndromic) NTDs is believed to be the result of a combination of genetic predisposition and environmental factors. Over 80 genes believed to be engaged in the neurulations have been identified during the investigation and research of the mouse models. Despite exhaustive research efforts, now spanning several decades, little is known about the actual genetic mechanisms governing the primary events involved in neural tube closure (NTC).     

Perioperative antibiotic prophylaxis in obstetrics and gynecology

This article reviews current opinions originating from Evidence Based Medicine regarding perioperative antibiotic prophylaxis in obstetrics and gynecology. The appropriate use of antibiotic prophylaxis constitutes one of the most effective preventive tools available for the obstetricians and gynecologists. Lack of antibiotic prophylaxis or their improper use may result in serious iatrogenic harm with potential medical but also economic and legal consequences.