Drug and Alcohol Rehabilitation: Monitoring Photosensitizer Uptake Using Two Photon Fluorescence Lifetime Imaging Microscopy.

Monitoring photosensitizer uptake using two photon fluorescence lifetime imaging microscopy.

Filed under: Drug and Alcohol Rehabilitation

Theranostics. 2012; 2(9): 817-26
Yeh SC, Diamond KR, Patterson MS, Nie Z, Hayward JE, Fang Q

Photodynamic Therapy (PDT) provides an opportunity for treatment of various invasive tumors by the use of a cancer targeting photosensitizing agent and light of specific wavelengths. However, real-time monitoring of drug localization is desirable because the induction of the phototoxic effect relies on interplay between the dosage of localized drug and light. Fluorescence emission in PDT may be used to monitor the uptake process but fluorescence intensity is subject to variability due to scattering and absorption; the addition of fluorescence lifetime may be beneficial to probe site-specific drug-molecular interactions and cell damage. We investigated the fluorescence lifetime changes of Photofrin(®) at various intracellular components in the Mat-LyLu (MLL) cell line. The fluorescence decays were analyzed using a bi-exponential model, followed by segmentation analysis of lifetime parameters. When Photofrin(®) was localized at the cell membrane, the slow lifetime component was found to be significantly shorter (4.3 ± 0.5 ns) compared to those at other locations (cytoplasm: 7.3 ± 0.3 ns; mitochondria: 7.0 ± 0.2 ns, p < 0.05). HubMed – drug


Hwangryun-Haedok-Tang Fermented with Lactobacillus casei Suppresses Ovariectomy-Induced Bone Loss.

Filed under: Drug and Alcohol Rehabilitation

Evid Based Complement Alternat Med. 2012; 2012: 325791
Shim KS, Kim T, Ha H, Cho CW, Kim HS, Seo DH, Ma JY

Hwangryun-haedok-tang (HRT) is the common recipe in traditional Asian medicine, and microbial fermentation is used for the conventional methods for processing traditional medicine. We investigated the inhibitory effect of the n-butanol fraction of HRT (HRT-BU) and fHRT (fHRT-BU) on the RANKL-induced osteoclastogenesis in bone-marrow-derived macrophages. mRNA expression of osteoclastogenesis-related genes were evaluated by real-time QPCR. The activation of signaling pathways was determined by western blot analysis. The marker compounds of HRT-BU and fHRT-BU were analyzed by HPLC. The inhibitory effect of HRT or fHRT on ovariectomy-induced bone loss were evaluated using OVX rats with orally administered HRT, fHRT (300, 1000?mg/kg), or its vehicle for 12 weeks. fHRT-BU significantly inhibited RANKL-induced osteoclastogenesis, and phosphorylation of p38, IKK?/?, and NF-?Bp65 compared to HRT-BU. In addition, fHRT-BU also significantly inhibited the mRNA expression of Nf?b2, TNF-?, NFATc1, TRAP, ATPv0d2, and cathepsin K. Furthermore, administration of fHRT had a greater effect on the increase of BMD, and greater improved bone microstructure of the femora than that of HRT in ovariectomy rats. This study demonstrated that bacterial fermentation enhances the inhibitory effect of HRT on osteoclastogenesis and bone loss. These results suggest that fermented HRT might have the beneficial effects on bone disease by inhibiting osteoclastogenesis.
HubMed – drug


Research progress on criteria for discontinuation of EGFR inhibitor therapy.

Filed under: Drug and Alcohol Rehabilitation

Onco Targets Ther. 2012; 5: 263-70
Zhuang HQ, Yuan ZY, Wang J, Wang P, Zhao LJ, Zhang BL

The clinical success of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) as therapeutic agents has prompted great interest in their further development and clinical testing for a wide variety of malignancies. However, most studies have focused on the efficacy of TKI, and few studies have been done on the criteria for their discontinuation. The current standard for drug discontinuation is “until progression”, based on change in tumor size. However, tumor size is not related to the gene expression which determines the efficacy of TKI in the final analysis, and it is also difficult to make a thorough and correct prediction based on tumor size when the TKI is discontinued. Nevertheless, clinical evaluation of the criteria for TKI discontinuation is still in its early days. Some promising findings have started to emerge. With the improving knowledge of EGFR and its inhibitors, it is expected that the criteria for discontinuation of EGFR inhibitor therapy will become clearer.
HubMed – drug


Carbon dioxide accumulation during analgosedated colonoscopy: Comparison of propofol and midazolam.

Filed under: Drug and Alcohol Rehabilitation

World J Gastroenterol. 2012 Oct 14; 18(38): 5389-96
Heuss LT, Sugandha SP, Beglinger C

To characterize the profiles of alveolar hypoventilation during colonoscopies performed under sedoanalgesia with a combination of alfentanil and either midazolam or propofol.Consecutive patients undergoing routine colonoscopy were randomly assigned to sedation with either propofol or midazolam in an open-labeled design using a titration scheme. All patients received 4 ?g/kg per body weight alfentanil for analgesia and 3 L of supplemental oxygen. Oxygen saturation (SpO(2)) was measured by pulse oximetry (POX), and capnography (PcCO(2)) was continuously measured using a combined dedicated sensor at the ear lobe. Instances of apnea resulting in measures such as stimulation of the patient, a chin lift, a mask maneuver, or withholding of sedation were recorded. PcCO(2) values (as a parameter of sedation-induced hypoventilation) were compared between groups at the following distinct time points: baseline, maximal rise, termination of the procedure and 5 min after termination of the procedure. The number of patients in both study groups who regained baseline PcCO(2) values (± 1.5 mmHg) five minutes after the procedure was determined.A total of 97 patients entered this study. The data from 14 patients were subsequently excluded for clinical procedure-related reasons or for technical problems. Therefore, 83 patients (mean age 62 ± 13 years) were successfully randomized to receive propofol (n = 42) or midazolam (n = 41) for sedation. Most of the patients were classified as American Society of Anesthesiologists (ASA) II [16 (38%) in the midazolam group and 15 (32%) in the propofol group] and ASA III [14 (33%) and 13 (32%) in the midazolam and propofol groups, respectively]. A mean dose of 5 (4-7) mg of IV midazolam and 131 (70-260) mg of IV propofol was used during the procedure in the corresponding study arms. The mean SpO(2) at baseline (%) was 99 ± 1 for the midazolam group and 99 ± 1 for the propofol group. No cases of hypoxemia (SpO(2) < 85%) or apnea were recorded. However, an increase in PcCO(2) that indicated alveolar hypoventilation occurred in both groups after administration of the first drug and was not detected with pulse oximetry alone. The mean interval between the initiation of sedation and the time when the PcCO(2) value increased to more than 2 mmHg was 2.8 ± 1.3 min for midazolam and 2.8 ± 1.1 min for propofol. The mean maximal rise was similar for both drugs: 8.6 ± 3.7 mmHg for midazolam and 7.4 ± 3.2 mmHg for propofol. Five minutes after the end of the procedure, the mean difference from the baseline values was significantly lower for the propofol treatment compared with midazolam (0.9 ± 3.0 mmHg vs 4.3 ± 3.7 mmHg, P = 0.0000169), and significantly more patients in the propofol group had regained their baseline value ± 1.5 mmHg (32 of 41 vs 12 of 42, P = 0.0004).A significantly higher number of patients sedated with propofol had normalized PcCO(2) values five minutes after sedation when compared with patients sedated with midazolam. HubMed – drug


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