Stress-opioid interactions: a comparison of morphine and methadone

The utility of methadone and morphine for analgesia and of methadone for substitution therapy for heroin addiction is a consequence of these drugs acting as opioid receptor agonists.We compared the cataleptogenic and antinociceptive effects of single subcutaneous doses of methadone hydrochloride (1–4 mg/kg) and morphine sulfate (2.5–10 mg/kg) using catalepsy and hot-plate tests, and examined the effects of the highest doses of the drugs on Fos protein expression in selected brain regions in male Sprague-Dawley rats. Methadone had greater cataleptogenic and analgesic potency than morphine. Fos immunohistochemistry revealed substantial effects on the Fos response of both the stress induced by the experimental procedures and of the drug exposure itself. There were three response patterns identified: 1) drug exposure, but not stress, significantly elevated Fos-positive cell counts in the caudate-putamen; 2) stress alone and stress combined with drug exposure similarly elevated Fos-positive cell counts in the nucleus accumbens and cingulate cortex; and 3) methadone and morphine (to a lesser extent) counteracted the stimulatory effect of nonpharmacological stressors on Fos protein expression in the somatosensory cortex barrel field, and Fos-positive cell counts in this region correlated negatively with both the duration of catalepsy and the latency time in the hot-plate test. The overlap between brain regions reacting to nonpharmacological stressors and those responding to exogenous opioids suggests that stress contributes to opioid-induced neuronal activation.     

Safety and efficacy of sequential i.v. to p.o. moxifloxacin versus conventional combination therapies for the treatment of community-acquired pneumonia in patients requiring initial i.v. therapy

To compare the efficacy of sequential i.v. to p.o. moxifloxacin with ceftriaxone ± azithromycin ± metronidazole for the treatment of patients with community acquired pneumonia (CAP), a multi-centered, prospective, randomized, open label study was performed. CAP patients were randomized to moxifloxacin (400 mg/d—at least one i.v. dose) or ceftriaxone (at least one dose of 2 g i.v. q.d. followed by cefuroxime 500 mg p.o. b.i.d.) ± azithromycin, ± metronidazole (cephalosporin/macrolide control: CMC). The primary endpoint was clinical response at test-of-cure (TOC) visit. Bacteriological response at TOC was the secondary endpoint. Clinical cure was found in 83.3% (90/108) of moxifloxacin patients and 79.6% (90/113) of control patients. Microbiological responses were 81.8% (18/22) for moxifloxacin and 60.7% (17/28) for CMC patients. Drug-related adverse events occurred in 18.0% of moxifloxacin and 16% of CMC patients. It is concluded that i.v. to p.o. moxifloxacin is as effective as CMC for treatment of CAP and is a reliable alternative antimicrobial therapy.     

Smoking and prognosis in women with breast cancer

The hypothesis was that smokers might have more aggressive types of breast cancer because of either delayed diagnosis or higher grade and hence have a worse prognosis. A cohort of breast cancer patients completed a lifestyle questionnaire at the time of diagnosis, including whether they were current smokers, ex-smokers or lifelong non-smokers. Ex-smokers were asked when they had stopped. The participants were 166 women with stage I/II invasive breast cancer diagnosed between October 1984 and March 1987. Participants were divided into three groups: current smokers, ex-smokers and non-smokers. Survival curves were produced by using Cox proportional hazards analysis, with outcome variables for overall and breast cancer-specific survival together with distant relapse-free survival. Smoking was the third most important predictor of distant relapse-free, breast cancer-specific and overall survival after stage and age at diagnosis. These results suggest that smokers are not only more likely to die of other diseases, but also have a higher mortality from breast cancer, compared with those with the disease who have never smoked. The best prognosis, however, was found in those who had given up smoking.     

Fine needle aspiration cytology of palpable breast lesions.

Fine needle aspiration cytology is a safe diagnostic technique for breast cancer and can identify certain benign lesions, which can be excised without affecting surrounding tissue. The combination of experienced operator and cytologist can yield high sensitivity and specificity, together with important prognostic information.     

Prevention of recognition memory loss and moderation of mitochondrial dynamic tendency toward fusion by flavone derivatives in Aβ-injected rats: a comparison between two flavonoids with different polarity

Growing evidence sheds light on the use of flavonoids as the promising alternatives for the treatment of chronic conditions, including cancer and neurodegenerative disorders. Accordingly, in the present study, we aimed at evaluating the effects of oral intake of two structurally different flavonoids 5-hydroxy-6,7,4?-trimethoxyflavone (flavone 1) and 5,7,4?-trihydroxyflavone (flavone 2) on recognition memory, hippocampal protein level of immediate early gene cFos and mitochondrial dynamic markers in Amyloid β (Aβ)-injected rats. Recognition aspect of memory and level of proteins were measured using novel object recognition test and Western blot, respectively. Our data indicated that even though flavone 1 was more effective than flavone 2 to prevent memory impairment, feeding with both flavones alleviated memory in Aβ-injected rats. Furthermore, in flavones-administered rats, mitochondrial dynamic balancing returned to the control level by the decline in Dynamin-related protein-1 protein level, a known marker for mitochondrial fission, and elevation in protein level of mitochondrial fusion factors Mitofusins 1 and 2. In parallel with behavior results, flavone 1 was more effectual on mitochondrial dynamic moderating. The more neuroprotective effects of flavone 1 could be attributed to its methylated structure leading to crossing of the blood-brain barrier with ease and metabolic stability and bioactivity.     

Efficacy and safety of pegylated interferon in children and adolescents infected with chronic hepatitis C: a preliminary study

This study researches the efficacy and safety of pegylated interferon alpha-2a (pegIFNα-2a) in Egyptian children and adolescents diagnosed with hepatitis C virus. Thirty patients were enrolled to receive pegIFN once a week with ribavirin twice daily for 12 weeks; viral load and experienced adverse effects were then assessed. Of the 30 patients, 16 (53.33%) were cleared from the virus, showing early virologic response (EVR). Three patients (10%) showed a 2-log reduction by week 12, with an overall early response rate of 63.33%. Three patients who showed EVR after 4 weeks relapsed by week 12. Levels of serum alanine aminotransferase (ALT) normalized at week 12. Adverse events included fever, myalgia, headache, flu-like symptoms, fatigue, anemia, and leucopenia; 63.33% of the patients showed significant reduction in their body weight. Although the patients showed a reduction in average body mass index, this reduction was not significant. Hemoglobin values decreased within the first 2 weeks and then stabilized but not back to baseline. A significant reduction in the level of absolute neutrophil count (ANC) was observed by the 4th week and started to improve by the 12th week. Of the recruited patients, 29.4% were subjected to IFN dose reduction. None of the patients with neutropenia developed serious infection or sepsis. The authors concluded that pegIFN plus ribavirin therapy is promising when tested on Egyptian children.