Treatment of bone and soft tissue infections with teicoplanin

The use of teicoplanin was evaluated in a group of 33 patients, which included 18 prosthetic infections, seven with osteomyelitis, five skin and soft tissue infections, and three cases of septic arthritis. The bacterial pathogens isolated were 27 isolates of Staphylococcus aureus (methicillin sensitive 18; methicillin resistant 9), Staph. hominis (2), Staph. epidermidis (1), Staph. haemolyticus (2), Enterococcus faecalis (1), Streptococcus pyogenes (1), Peptococcus spp. (1). Eleven patients had polymicrobial infections (Gram-positive plus Gram-negative and/or anaerobic bacteria). In ten cases (nine polymicrobial infections) teicoplanin was used in combination with other antibiotics. Teicoplanin was administered intravenously 400 mg every 24 h in 26 cases, 200 mg every 24 h in six cases and 600 mg every 24 h in one case. The duration of the treatment ranged from 9 to 73 days with a mean of 27.3. Efficacy was evaluable in 30 patients, because in three patients treatment was stopped because of adverse reactions. Cure or improvement was noted in 28 patients (93%). Bacteriological cure occurred in 25 patients (83.3%).     

Is alcohol consumption a risk factor for weight gain and obesity?

Alcohol represents an important source of energy. Despite its comparatively high energy content of 7.1 g/kcal, it is still controversial whether moderate amounts of alcohol represent a risk factor for weight gain and obesity. Epidemiologic data showed a positive, negative, or no relationship between alcohol intake and body weight. Despite the difficulty in assessing alcohol intake as well as controlling for different confounders of the energy-balance equation, the conflicting epidemiologic data can be explained in most instances. Every component of the energy-balance equation is affected by the ingestion of alcohol. Moderate amounts of alcohol enhance energy intake due to the caloric content of the alcohol as well as its appetite-enhancing effects. Alcohol-induced thermogenesis is approximately 20% in healthy nonalcoholic subjects, i.e., moderate alcohol consumers, which is higher than for other energy substrates but considerably lower than in heavy alcohol consumers. This would suggest that a major fraction of the alcohol energy represents a navailable energy source for ATP synthesis in moderate non-daily alcohol consumers. Experimental evidence from several metabolic studies showed a suppression of lipid oxidation by alcohol and thus the enhancement of a positive fat balance. The nonoxidized fat is preferentially deposited in the abdominal area. The experimental metabolic evidence suggests that the consumption of moderate amounts of alcohol has to be accounted for in the energy-balance equation and may represent a risk factor for the development of a positive energy balance and thus weight gain. In the heavy alcohol consumer and eventually also in daily moderate alcohol consumers, a larger fraction of the alcohol energy might not be an available source of energy due to the induction of the microsomal ethanol-oxidizing system (MEOS). Experimental data in combination with epidemiologic findings suggest that alcohol energy counts more in moderate nondaily alcohol consumers than in some moderate daily and all heavy consumers. Accordingly the question is not "Whether alcohol calories do count" but "How much do alcohol calories count?". There seems to be a large individual variability according to the absolute amount of alcohol consumed, the drinking frequency as well as genetic factors. Presently it can be said that alcohol calories count more in moderate nondaily consumers than in daily (heavy) consumers. Further, they count more in combination with a high-fat diet and in overweight and obese subjects.     

LYSOSOMAL ACID HYDROLASES IN MICE INFECTED WITH BCG

Experiments are reported dealing with the increase of lysosomal acid hydrolases induced by BCG infection. Acid hydrolases were determined quantitatively in peritoneal MP, liver homogenate, and plasma of normal and BCG-infected mice. A significant increase of acid phosphatase, β-glucuronidase, and cathepsin was found in MP and liver homogenate of BCG-infected mice. In plasma also a significant increase of acid phosphatase and β-glucuronidase was noticed. The results of the determination of the enzymes in centrifugally separated subcellular fractions of liver homogenate indicated clearly that the acid hydrolases associated mainly with the "large granular" fraction, which consists of mitochondria, lysosomes, and microsomes and that infection with BCG caused significant increase of the enzymes specifically in this fraction. Differences in the pattern of location among centrifugally separated fraction of liver homogenate were observed between acid phosphatase and the other two acid hydrolases. MP cultured in vitro doubled their acid phosphatases content within 24 hours, whereas β-glucuronidase rather decreased in the same cells.     

Expression dynamics of NADPH oxidases during early zebrafish development

Nicotinamide dinucleotide phosphate oxidases (NOX) control various cellular signaling cascades. In the nervous system, there is recent evidence that NOX‐derived reactive oxygen species (ROS) regulate neurite outgrowth, regeneration, and stem cell proliferation; however, a comprehensive NOX gene expression analysis is missing for all major model systems. Zebrafish embryos provide an excellent model system to study neurodevelopment and regeneration because they develop quickly and are well suited for in vivo imaging and molecular approaches. Although the sequences of five NOX genes (nox1, nox2/cybb, nox4, nox5, and duox) have been identified in the zebrafish genome, nothing is known about their expression pattern. Here, we used quantitative polymerase chain reaction combined with in situ hybridization to develop a catalog of nox1, nox2/cybb, nox5, and duox expression in zebrafish during early nervous system development from 12 to 48 hours post fertilization. We found that expression levels of nox1, nox5, and duox are dynamic during the first 2 days of development, whereas nox2/cybb levels remain remarkably stable. By sectioning in situ hybridized embryos, we found a pattern of broad and overlapping NOX isoform expression at 1 and 1.5 days post fertilization. After 2 days of development, a few brain regions displayed increased NOX expression levels. Collectively, these results represent the first comprehensive analysis of NOX gene expression in the zebrafish and will provide a basis for future studies aimed at determining the functions of NOX enzymes in neurodevelopment and regeneration. J. Comp. Neurol. 524:2130–2141, 2016. © 2015 Wiley Periodicals, Inc.     

Teicoplanin in the treatment of infections by staphylococci, Clostridium difficile and other gram-positive bacteria

Eighty-three episodes of Gram-positive infection in 82 patients were treated with teicoplanin in an open study. Infectious episodes included endocarditis (6 cases), bacteraemia (7), osteomyelitis (8), pseudomembranous colitis (13), cellulitis (11), urinary tract infection (5), pneumonia (1), wound and post-surgical infections (9) and erysipelas (23). Four patients affected by an overwhelming Gram-positive infection as well as eight cases of Gram-positive-Gram-negative mixed infections received teicoplanin in combination with other antibiotics. The average duration of treatment was 16 days (range 5-70). In pseudomembranous colitis teicoplanin was given by mouth for ten days. Staphylococcus aureus (11 methicillin-sensitive and 13 methicillin-resistant strains) and Clostridium difficile (13 isolates) were the most frequent pathogens. Overall 89% (74/83) of the infections were cured, 3.6% (3/83) improved and 3.6% (3/83) failed. Relapse and superinfection were observed in 2.4% (2/83) and 1.2% (1/83) episodes respectively. All pseudomembranous colitis cases were clinically cured and C. difficile was eradicated in all but one patient. The MIC range, MIC50 and MIC90 (mg/l) of teicoplanin for C. difficile were less than 0.125-0.250, less than 0.125 and 0.250 respectively. Pharmacokinetic studies in patients given a single iv daily maintenance dose of 400 mg showed that the steady-state trough teicoplanin concentrations in serum were reached on day 8. Assays of skin-subcutaneous tissue biopsies showed that teicoplanin penetrated well into these structures. Side effects were observed in six of the 82 treated patients (7.3%) and teicoplanin had to be discontinued in four cases. The results of the study show that teicoplanin is a safe and useful new agent for the treatment of infections caused by Gram-positive organisms, including methicillin-resistant staphylococci and C. difficile.