Phagocyte-specific calcium-binding S100 proteins as clinical laboratory markers of inflammation

The EF-hand homolog family of S100 proteins comprises the largest group of calcium-binding proteins. Within this S100 family, the phagocyte-specific calcium-binding proteins are pro-inflammatory molecules expressed and secreted by phagocytes, which play a pivotal role within the innate immune system. Although the exact biological functions of these proteins still remain to be defined in greater detail, there is evidence that they are involved in a pro-inflammatory axis associated with various inflammatory conditions. The three members of this group, S100A8, S100A9 and S100A12 are overexpressed at local sites of inflammation. High concentrations are found in synovial fluid, sputum, stool and blood plasma/serum during inflammation. Both the S100A8/S100A9 complex and S100A12 have been proven to be useful as diagnostic markers of inflammation especially in non-infectious inflammatory diseases such as arthritis, chronic inflammatory lung and bowel disease. They indicate phagocyte activation more sensitively than conventional parameters of inflammation. As a consequence, there is a strong correlation to the inflammation of various acute and chronic disorders, making these proteins sensitive parameters for the monitoring of disease activity and response to treatment in individual patients. The phagocyte-specific S100 proteins are able to indicate minimal residual inflammation, which is not detected by other diagnostic tests, and they may even be prospective markers for the outcome of patients. In this review, pro-inflammatory functions of S100 proteins and their usefulness as biomarkers of inflammation are presented.     

Acceptance of medical hypnosis by oral and maxillofacial patients

Prognosis in surgical treatment of diseases of the oral and maxillofacial region under local anesthesia is quite commonly restricted by compliance by the patient. An alternative approach, medical hypnosis, has not been used in oral and maxillofacial surgery to any significant degree. As such, hypnosis treatment also depends to a great extent on the cooperation of the patient, and it would seem advisable to collect information concerning the individual motivation for accepting such a treatment option. The questionnaire consisted of 21 questions and was handed out to patients of the department. A total of 310 questionnaires were evaluated statistically, and the result shows a high level of acceptance of medical hypnosis by patients being treated surgically in the oral and maxillofacial region. The authors conclude that the effectiveness of this treatment option should be examined in clinical studies.     

A mutation in Escherichia coli DNA gyrase conferring quinolone resistance results in sensitivity to drugs targeting eukaryotic topoisomerase II

Fluoroquinolones are broad-spectrum antimicrobial agents that target type II topoisomerases. Many fluoroquinolones are highly specific for bacterial type II topoisomerases and act against both DNA gyrase and topoisomerase IV. In Escherichia coli, mutations causing quinolone resistance are often found in the gene that encodes the A subunit of DNA gyrase. One common site for resistance-conferring mutations alters Ser83, and mutations to Leu or Trp result in high levels of resistance to fluoroquinolones. In the present study we demonstrate that the mutation of Ser83 to Trp in DNA gyrase (Gyr(S83W)) also results in sensitivity to agents that are potent inhibitors of eukaryotic topoisomerase II but that are normally inactive against prokaryotic enzymes. Epipodophyllotoxins, such as etoposide, teniposide and amino-azatoxin, inhibited the DNA supercoiling activity of Gyr(S83W), and the enzyme caused elevated levels of DNA cleavage in the presence of these agents. The DNA sequence preference for Gyr(S83W)-induced cleavage sites in the presence of etoposide was similar to that seen with eukaryotic type II topoisomerases. Introduction of the Gyr(S83W) mutation in E. coli strain RFM443-242 by site-directed mutagenesis sensitized it to epipodophyllotoxins and amino-azatoxin. Our results demonstrate that sensitivity to agents that target topoisomerase II is conserved between prokaryotic and eukaryotic enzymes, suggesting that drug interaction domains are also well conserved and likely occur in domains important for the biochemical activities of the enzymes.     

Cloned horse pregnancies produced using adult cumulus cells

The objectives of the present study were to: (1) clone horses using adult cumulus cells; and (2) determine whether the cumulus cell donor affected the outcome. In vivo-matured cumulus-oocyte complexes were obtained using transvaginal ultrasound-guided follicle aspiration; oocytes were used as cytoplasts, whereas cumulus cells (from one of three different mares) were used as donor cells. Immediately following nuclear transfer and activation procedures, cloned embryos were transferred surgically to the oviduct of recipient mares (n = 2-5 embryos per recipient) that had ovulated within 24 h prior to the transfer. An initial pregnancy examination was performed between Days 14 and 16 (Day 0 = surgery); subsequent examinations were then performed every 7-10 days. A total of 136 follicles were aspirated in 96 mares, from which 72 oocytes were recovered (53%). Sixty-two cloned embryos were transferred to recipient mares, which resulted in seven (11.3%) ultrasonographically detectable conceptuses between Days 14 and 16. All seven conceptuses were lost spontaneously between Days 16 and 80. Cumulus cells from Mare 160 tended (P = 0.08) to result in a higher embryo survival rate than cumulus cells from Mare 221 (4/17 v. 1/25 respectively). To our knowledge, this is the first report documenting the establishment of cloned equine pregnancies derived from adult cumulus cells.     

Body composition and bone measurements in intra-uterine growth retarded and early postnatally undernourished male and female rats at the age of 6 months: comparison with puberty

Undernutrition in early life may permanently change body structure, physiology and metabolism and leads to chronic diseases in later life. To test whether malnutrition during different critical time periods around birth in the rat has long-lasting effects on body composition and skeletal growth, we examined body weight and body composition in pubertal rats and adult rats of 6 months after pre- and postnatal malnutrition. Prenatal malnutrition or intra-uterine growth retardation (IUGR) was induced by ligation of the uterine arteries on day 17 of gestation and postnatal food restriction (FR) by litter enlargement to 20 pups per mother from day 2 after birth until weaning (day 24). Pubertal markers were balanopreputial separation (BPS) in the male and vaginal opening (VO) in the female. IUGR as well as FR resulted in a persistent growth retardation. From birth in IUGR rats and from day 4 after birth in FR rats until 6 months of age body weight in male and female rats was significantly lower compared with controls (P < 0.01 and P < 0.05). Although total body bone mineral content (TBBMC) did not differ between male IUGR rats and controls at BPS, at the age of 6 months TBBMC was significantly lower (P < 0.01) compared with controls. At BPS as well as at 6 months of age, TBBMC was significantly lower in male FR rats compared with controls (P < 0.05 and P < 0.01). In the female IUGR rats TBBMC was significantly lower compared with controls at VO (P < 0.01) and 6 months (P < 0.05). TBBMC in the female FR rats was significantly lower at VO (P < 0.01), but did not differ from controls at the age of 6 months. For both IUGR and FR male and female rats these differences disappeared after adjusting for body weight. Body composition in terms of total fat mass, percentage fat and percentage lean did not differ from controls in male and female IUGR rats at 6 months and the same results were observed in the female FR rats. However, in the male FR rats, total fat mass and percentage fat were significantly lower compared with controls (P < 0.01 and P < 0.05), while the percentage lean mass was significantly higher (P < 0.05). We conclude that different critical time periods of malnutrition around birth have different effects later in life on growth, which do not disappear at least after 6 months of life. With respect to body composition, only in the FR male rats, differences are found in total fat mass and the balance of percentage fat mass and lean mass. At time of puberty and at the age of 6 months bone mass adjusted for body weight does not seem to be affected by perinatal undernutrition.     

Dietary lipids and vascular function: UK Food Standards Agency workshop report

The UK Food Standards Agency convened a group of expert scientists to review current research investigating the effect of dietary lipids on vascular function. The workshop highlighted the need for intervention studies to be sufficiently powered for these measures and that they should be corroborated with other, more validated, risk factors for CVD. Work presented at the workshop suggested a beneficial effect of long-chain n-3 PUFA and a detrimental effect of trans fatty acids. The workshop also considered the importance of the choice of study population in dietary intervention studies and that "at risk" subgroups within the general population may be more appropriate than subjects that are unrepresentatively healthy.     

Potential savings from reducing inequalities in health

BACKGROUND: Numerous studies have established that socio-economic position is positively related to health status, but we know little about the real costs of these differences across an entire population. This paper estimates the potential savings in morbidity and dollars from reducing the inequalities in health among Winnipeg residents. METHODS: We measure excess morbidity by examining rates of premature death, hip fracture, and heart attack according to the relative affluence of the Winnipeg neighbourhood. We also assess the total expenditures on physician and hospital care by neighbourhood of residence. We then estimate the savings that could have been achieved if 1 ) the health of the two poorest quintiles had been raised to the level of the middle quintile, and 2) the health of the poorest four quintiles had been raised to the level of the top quintile. RESULTS: Thirty-seven percent of Winnipeg's premature deaths, 22% of the heart attacks, 20% of the hip fractures and 15% of total expenditures on hospitals and physicians ($62 million in 1999 dollars) could have been avoided if residents of the less wealthy 80% of neighbourhoods enjoyed health similar to those in the wealthiest neighbourhoods. CONCLUSION: The potential savings from reducing the socio-economic-related differences in health are high, whether they are measured in terms of morbidity or dollars. Research is needed to determine the extent to which these potential savings are achievable.     

The force required to remove the frameless 0-suture IUD anchoring system: comparison between pre- and postmenopausal women

OBJECTIVE: The objective of this short communication is to measure and compare the force needed to remove the implanted "0-suture" GyneFix intrauterine contraceptive device (IUD) and the "0-suture" FibroPlant trade mark -LNG intrauterine system (IUS) from the uterus of pre- and postmenopausal women. STUDY DESIGN: A nonrandomized comparative study in 119 pre- and postmenopausal women. A dynamometer (Pesola) was used to measure the removal force in newtons. RESULTS: The results of this study show a mean removal force of 8.5 and 9.5 newtons, respectively (range, 3-11 and 4.5-11), in pre- and postmenopausal women, which is significantly different (p = 0.003). CONCLUSIONS: The force needed to remove the IUD/IUS anchored in the myometrium of the uterine fundus of pre- and postmenopausal women is higher than the removal force found in previous studies in which the IUD consisted of a slightly thinner anchoring thread (00 instead of 0 suture). The statistically significantly different removal force between the two groups has no clinical implications. The difference may reflect the increased compactness of the uterine tissue in the postmenopausal uterus.