Once-A-Day therapy for sinusitis: A comparison study of cefixime and amoxicillin

The efficacy and safety of a once-a-day antibiotic in the treatment of sinusitis was studied. Two randomly assigned groups were treated with either once-a-day cefixime, a third generation cephalosporin, or amoxicillin three times a day. One hundred and fourteen patients were evaluated with antral punctures, microbiologic evaluation, and radiographic studies. Cultures revealed 40% gram-negative organisms, 48% gram-positive, and 12% anaerobes. The most common bacteria were Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus and viridans group streptococci. Ninety-four percent of the cefixime group were cured compared with 96% of the amoxicillin group. Staphylococcus resistance was a problem in both groups, necessitating an occasional change to amoxicillin-clavulanate potassium in the amoxicillin group. Once-a-day antibiotics offer the potential for improved compliance in the treatment of sinusitis. Cefixime offers an additional benefit of covering β-lactamase producing strains of bacteria which are increasing in incidence and resistant to many penicillins.     

Role of R-(-)-deprenyl in adhesion of neuronal and non-neuronal cells

Role of R-(-)-deprenyl in adhesion of neuronal and non-neuronal cells. The beneficial effect of the anti-parkinsonian monoamine oxidase-B inhibitor, R-(-)-deprenyl has been shown in a number of different diseases, such as Parkinson's and Alzheimer's disease, atherosclerosis or tumor formation. The role of the cytoskeleton, the main component of cell adhesion, has been suggested in the development of these diseases. Nevertheless, the effect of the drug on cell adhesion has never been examined. In the present study, the authors studied the effect of R-(-)-deprenyl on cell-cell adhesion of neuronal (PC12, rat phaeochromocytoma) and non-neuronal (NIH3T3, NIH3T3/EGFR, NIH3T3/EGFR-e3B1 mouse embryo fibroblasts, and 5180 mouse sarcoma) cells using cell association assay. R-(-)-deprenyl treatment resulted in a cell type- and concentration-dependent increase in cell-cell adhesion of PC12 cells, which contain no monoamine oxidase-B, and we observed the same effect in NIH3T3 cells at concentrations lower than those needed for monoamine oxidase-B inhibition. Interestingly, R-(-)-deprenyl increased cell-cell adhesion of tumor cell lines as well. The effect of R-(-)-deprenyl was not reversible during a 24-hour recovery period. At the same time, the monoamine oxidase-B inactive isomer of the drug, S-(+)-deprenyl had no effect on cell-cell adhesion in PC12 and NIH3T3 cells. In this study, the authors described a new, monoamine oxidase-B independent effect of R-(-)-deprenyl on cell-cell adhesion both in neuronal and non neuronal cells. The authors' results with S-(+)-deprenyl suggest that the sterical structure of the drug is an important factor of the observed effect, which is probably a consequence of an irreversible change in the cells.     

Calpain-3 gene defect causing limb gird muscular dystrophy in a Hungarian family

Limb gird muscular dystrophies (LGMD2) are a clinically and genetically heterogeneous group of hereditary diseases with autosomal recessive trait, characterized by progressive atrophy and weakness predominantly in the proximal limb muscles. The authors present clinical, histological, immunohistochemical and immunoblot results of two sisters suffering from so far unclassified autosomal recessive limb girdle muscular dystrophy. Haplotype analysis for genes possibly involved in autosomal recessive limb girdle muscular dystrophies was performed in the genetically informative family. All of the results pointed to a molecular genetic defect of the calpain-3 (CAPN3) gene. Direct sequencing of the CAPN3 gene revealed compound heterozygous state for two mutations previously described in association with limb girdle muscular dystrophy, proving pathogenicity. The authors would like to emphasize the importance of the above described combined strategy in diagnosing limb girdle muscular dystrophies.     

Recurrent perivascular inflammation induced by lipopolysaccharide (endotoxin) results in the formation of atheromatous lesions in vivo

Bacteria and viruses are suspected to induce arteriosclerosis; however, most investigators have focused on coincidences rather than causal relationships. The aim of this work was to establish a rabbit model in which the vessel reaction to local perivascular injection of defined bacterial products can be analyzed. A total of 23 rabbits were randomized to four groups. Groups A and B were fed a normal diet, groups C and D were fed a cholesterol-enriched diet. Groups A and C were treated with a single perivascular injection of bacterial lipopolysaccharide (LPS, endotoxin) placed next to auricular, carotid and femoral arteries, and sodium chloride placed next to the contralateral arteries (control). Group B and D animals were treated with repeated perivascular injections over 90 days. Vascular tissues (n=116 treated segments of 23 rabbits) were analyzed using morphometry at histology, and using immunohistochemistry to detect macrophages, lymphocytes and vascular smooth muscle cells. LPS treatment resulted in transient focal intima thickening. After single LPS application, no increase in atheromatous lesion formation was observed in comparison with controls (group C, lesion area index 0.031+/-0.012 vs 0.015+/-0.006, P=1.0). Repeated LPS application resulted in significant atheromatous lesion formation compared with saline control (group D, lesion area index 0.148+/-0.049 vs 0.008+/-0.006, P=0.003) in hypercholesterolemic rabbits. Repeated LPS inflammation in normocholesterolemic did not lead to atheromatous lesion formation (intima media ratio 0.04+/-0.01 vs 0.04+/-0.007, P=1.0). Single perivascular administration of low-dose bacterial LPS resulted in transient focal intimal thickening, while significant increase in lesion formation occurred after repeated LPS application in cholesterol-fed animals. In conclusion, this animal model will allow the assessment of the impact of defined dosages of different bacterial pathogens onto the vascular wall in the context of atherogenesis. The atheromatous lesion-promoting effect of repeated perivascular administration of LPS supports the hypothesis that bacterial pathogens may be involved in atherogenesis.     

Cellular and physiological effects of soy flavonoids

Recent experimental and epidemiological studies have provided convincing evidence for a variety of health benefits derived from the consumption of soy and soy food products. For example, soy isoflavones are felt to protect against different cancers, cardiovascular disease, and bone loss. Many studies have demonstrated the effect of soy isoflavones on specific target molecules and signaling pathways, including but not limited to, cell proliferation and differentiation, cell cycle regulation, apoptosis, angiogenesis, cell adhesion and migration, metastasis, and activity of different enzymes. Isoflavones also share structural homologies with estrogens and are therefore classified as phytoestrogens with weak estrogenic properties. Since isoflavones bind to estrogen receptors (ER alpha and ER beta), they are considered to be possible estrogen receptor modulators. However, isoflavones can also exert biological effects independent of their phytoestrogenic activities. Recent studies suggest beneficial health effects of soy and recommend increasing the intake of isoflavone-rich soy protein to the level of intake commonly used in Asian countries.     

Regional distribution of proteinase K-resistant alpha-synuclein correlates with Lewy body disease stage

Lewy bodies (LBs) containing alpha-synuclein (alphaSYN) fibrils are the hallmark lesions of Parkinson disease, dementia with LBs, and related neurodegenerative diseases. Here we have investigated the susceptibility to proteolysis of alphaSYN from brain samples of patients with different subtypes of LB diseases. While soluble alphaSYN was completely degradable in all samples, the affected brain regions additionally contained insoluble, proteinase K (PK)-resistant alphaSYN. In brainstem-predominant subtype LB disease cases, PK-resistant alphaSYN was found in the medulla and substantia nigra, but not in cerebral cortex. In limbic subtype LB disease cases, PK resistance of alphaSYN spread to the cingulate and parahippocampal cortex, and further to the frontal cortex in neocortical subtype LB disease cases. Variable amounts of neuritic PK-resistant alphaSYN were found in the striatum of all cases. Thus, PK resistance of alphaSYN may be useful for the development of biomarkers of LB diseases.     

Structurally related mycotoxins ochratoxin A, ochratoxin B, and citrinin differ in their genotoxic activities and in their mode of action in human-derived liver (HepG2) cells: implications for risk assessment

To elucidate the effects of three structurally related mycotoxins, namely, ochratoxin A (OTA), ochratoxin B (OTB), and citrinin (CIT), on human health, we investigated their acute toxic, mitogenic, and genotoxic effects in the human-derived liver cell line (HepG2). These compounds are found in moldy foods in endemic areas of nephropathy, which is associated with urinary tract cancers. In agreement with previous experiments, we found that OTA causes a dose-dependent induction of micronuclei (MN) and DNA migration in the single-cell gel electrophoresis (SCGE) assay, which was statistically significant at concentrations of > or =5 microg/ml. In contrast, OTB was devoid of genotoxic activity under identical conditions, but the compound caused pronounced inhibition of cell division even at doses lower than OTA (10 microg/ml). CIT caused an effect similar to that of OTA in MN assays (significant at dose levels of > or =2.5 microg/ml) but was negative in the SCGE test. All compounds failed to induce mutations in Salmonella/microsome assays in strains TA 98 and TA 100 after addition of HepG2-derived enzyme homogenate (S9-mix). By use of DNA-centromeric probes we found that induction of MN by OTA involves chromosome breaking effects (55-60% of the MN were centromere negative), whereas CIT-induced MN were predominantly centromere positive (78-82%). Our findings indicate that OTB is devoid of genotoxic activity in human-derived cells and therefore probably not a genotoxic carcinogen in humans. In contrast, CIT was an equally potent inducer of MN in HepG2 cells as OTA, but this effect is caused by a different mechanism, namely, aneuploidy. Furthermore, our data suggest that combined exposure to structurally related mycotoxins that cause DNA damage via completely different mechanisms may significantly increase the cancer risk of humans consuming moldy foods.     

Hypothesis of regulation of hip joint cartilage activity by mechanical loading

Hypothesis of regulation of proteosynthetic activity of chondrocytes is suggested. A deformation of the cartilage caused by contact hip joint stress and consequent deformation of the chondrocytes are considered as main factors that could influence the metabolism of the cartilage.