Response of MG63 osteoblasts on bacterial challenge is dependent on the state of differentiation

The present in vitro study examines molecular processes that are relevant during bone homeostasis after Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis infection with a focus on the differentiation level of osteoblasts. Regenerative processes are often hindered by the recurrence of bacterial infections, which can ultimately provoke a severe destruction of bone tissue. To obtain more detailed insights into such a complex scenario, we have used undifferentiated MG63 osteoblast‐like cells as an experimental paradigm to examine the impact of two oral pathogens, A. actinomycetemcomitans and P. gingivalis, on proliferation, cytotoxicity and osteogenic differentiation. Cell culture experiments were performed to analyze cellular behavior. The level of genes interfering with bone tissue integrity (matrix metalloproteinases and their tissue inhibitors) and osteogenic markers (alkaline phosphatase, Runx2, human β‐defensin‐2) was compared in undifferentiated versus differentiated MG63 cells using real‐time polymerase chain reaction. Functional activity of matrix metalloproteinases was quantified by zymography. Western blot analysis was used to verify the phosphorylation state of mitogen‐activated protein kinases p38 and extracellular‐signal‐regulated kinases 1/2. When co‐cultured with undifferentiated MG63 cells, oral pathogens provoked distinct cellular effects. Only A. actinomycetemcomitans reduced cell proliferation, increased cell death, and induced osteogenic differentiation. A comparison of matrix metalloproteinase network stability in the presence of oral pathogens revealed a partial sensitivity towards P. gingivalis but not A. actinomycetemcomitans. So, beside the proof of concept that MG63 cells co‐cultured with oral pathogens can serve as an in vitro model for mimicking destructive and regenerative events after bacterial infections, our data indicate that double infections might counterbalance otherwise positive effects.     

Toremifene in the treatment of breast cancer

Although more widespread screening and routine adjuvant therapy has improved the outcome for breast cancer patients in recent years, there remains considerable scope for improving the efficacy, safety and tolerability of adjuvant therapy in the early stage disease and the treatment of advanced disease. Toremifene is a selective estrogen receptor modifier (SERM) that has been widely used for decades in hormone receptor positive breast cancer both in early and late stage disease. Its efficacy has been well established in nine prospective randomized phase III trials compared to tamoxifen involving more than 5500 patients, as well as in several large uncontrolled and non-randomized studies. Although most studies show therapeutic equivalence between the two SERMs, some show an advantage for toremifene. Several meta-analyses have also confirmed that the efficacy of toremifene is at least as good as that of tamoxifen. In terms of safety and tolerability toremifene is broadly similar to tamoxifen although there is some evidence that toremifene is less likely to cause uterine neoplasms, serious vascular events and it has a more positive effect on serum lipids than does tamoxifen. Toremifene is therefore effective and safe in the treatment of breast cancer. It provides not only a useful therapeutic alternative to tamoxifen, but may bring specific benefits.     

Respiratory viruses in children admitted to hospital in Edinburgh 1972-1985

The temporal incidence of respiratory viruses identified in children admitted to an Edinburgh hospital over a period of 14 years, 1972-1985, is described, Respiratory syncytial (RS) virus was identified most often, usually (but not in 1979 and 1985) with single peaks of activity in the winter months. Influenza virus infections were seen in the winter and spring but we failed to find evidence of interference between RS and influenza virus. Of the viruses studied, the parainfluenza viruses were the least predictable in their epidemiological behaviour. The results of this study are compared with those of others and the role of certain aspects of the weather is considered.     

Occurrence of Extended-Spectrum Betalactamases (ESBL) in Dutch Hospitals

Summary The prevalence of ESBL was determined among isolates of Escherichia coli (n = 571) and Klebsiella spp. (n = 196) collected during a 1-week study period in 8 university and 3 large regional laboratories all over the Netherlands. 18 isolates were positive for at least one of the screening tests used, i.e., VITEK-ESBL, E-test ESBL and MIC ratio of ceftazidime/ceftazidime-clavulanic acid, cefotaxime/cefotaxime-clavulanic acid. In 5 of these 18 putative ESBLs no betalactamase production was detectable. A TEM type was found in three E. coli and two Klebsiella spp. An SHV type was present in five Klebsiella spp. In one E. coli and one Klebsiella pneumoniae both enzymes were present. In one Klebsiella oxytoca neither of the two enzymes was present. Using PCR for both ESBL TEM and ESBL SHV, an SHV ESBL was found in one E. coli and four Klebsiella isolates. The mutations at position 238 and 240 were already described. In one E. coli isolate a TEM ESBL was found with three mutations, at position 21, 164 and 265. These mutations were already described in other ESBLs but not in this combination suggesting a new TEM ESBL. The overall prevalence of ESBL producing E. coli and Klebsiella spp. was less than 1% (6 out of 767). Received: December 14, 1998 · Accepted: September 19, 1999     

Declining testicular function with age. Hormonal and clinical correlates

Testicular endocrine function and androgen-dependent secondary sexual characteristics were assessed in 283 men 18 to 96 years of age. Mean serum total testosterone levels remained unchanged up to age 70 and declined thereafter. In 29 per cent of the men over 70 years of age total testosterone levels were below the lower limit of normal for young adults, In contrast, mean free or unbound testosterone levels declined after age 50 and were below the lower limit of normal for young adults in 40 per cent of the men over 70 years of age. Serum-luteinizing hormone and follicle-stimulating hormone levels showed a slight but steady rise after age 40 which became more abrupt after age 70. Serum gonadotropin levels were elevated in approximately 60 per cent of the men over 70 years of age.Mean testis length and volume were decreased in 78 per cent and 37 per cent, respectively, of the men over 60 years of age. Facial, pubic and axillary hair were also reduced in amount whereas the prostate was enlarged in 73 per cent of the elderly men. There appeared to be an inverse relationship in older men between testicular size and gonadotropin levels, and a direct relationship between testicular and prostatic sizes.It would appear that some degree of Leydig cell hypofunction commonly begins at around 45 to 50 years of age, becoming more pronounced after age 70. The concomitant elevation in serum gonadotropin levels at this time indicates that this is due to a primary decline in testicular function and is not secondary to pituitary hypofunction.