Substance P and human nasal mucociliary activity

Summary Substance P (SP), a potent inflammatory agent, has been found in sensory nerve fibres in the nasal mucosa in several experimental animals as well as in man. It may participate in the inflammatory response as part of the mucosal defence against foreign materials. In experimental animals SP has been found to increase mucociliary in airway mucosa. The present study was performed in order to find out the relationship between topically applied SP and nasal mucociliary function in humans. Thirteen healthy volunteers were challenged with 65 µg SP or placebo in a randomized cross over fashion and mucociliary transport time was determined each time using the saccharine dye test. The dose of SP was chosen after an open dose-response study. No statistically significant change in the mucociliary transport time was found after challenge with SP as compared to placebo. The possible reasons for this are discussed.     

Guidance of dopaminergic neuritic growth by immature astrocytes in organotypic cultures of rat fetal ventral mesencephalon.

Astrocytes, with their many functions in producing and controlling the environment in the brain, are of great interest when it comes to studying regeneration after injury and neurodegenerative diseases such as in grafting in Parkinson's disease. This study was performed to investigate astrocytic guidance of growth derived from dopaminergic neurons using organotypic cultures of rat fetal ventral mesencephalon. Primary cultures were studied at different time points starting from 3 days up to 28 days. Cultures were treated with either interleukin-1 beta (IL-1 beta), which has stimulating effects on astrocytic proliferation, or the astrocytic inhibitor cytosine arabinoside (Ara-C). Tyrosine hydroxylase (TH)-immunohistochemistry was used to visualize dopaminergic neurons, and antibodies against glial fibrillary acidic protein (GFAP) and S100 beta were used to label astrocytes. The results revealed that a robust TH-positive nerve fiber production was seen already at 3 days in vitro. These neurites had disappeared by 5 days. This early nerve fiber outgrowth was not guided by direct interactions with glial cells. Later, at 7 days in vitro, a second wave of TH-positive neuritic outgrowth was clearly observed. GFAP-positive astrocytic processes guided these neurites. TH-positive neurites arborized overlying S100 beta-positive astrocytes in an area distal to the GFAP-positive astrocytic processes. Treatment with IL-1 beta resulted in an increased area of TH-positive nerve fiber network. In cultures treated with Ara-C, neither astrocytes nor outgrowth of dopaminergic neurites were observed. In conclusion, this study shows that astrocytes play a major role in long-term dopaminergic outgrowth, both in axonal elongation and branching of neurites. The long-term nerve fiber growth is preceded by an early transient outgrowth of dopamine neurites.     

Hypoplasia of the Posterior Leaflet as a Rare Cause of Congenital Mitral Insufficiency

A bstract A rare case of congenital mitral insufficiency characterized by the hypoplasia of the posterior leaflet is reported. At operation, the mitral valve was successfully repaired by a ring annuloplasty, which created a satisfactory surface of coaptation between the anterior leaflet and the bulky posterior muscular structure. The presence of this posterior muscular structure represents a developmental arrest at the stage of conversion from muscular chordae and leaflets to thin connective structures.     

Psychosocial aspects of disease duration and control in young adults with type I diabetes

Self-report questionnaires completed by young adults with Type I diabetes were examined to determine if individuals differing in recent metabolic control (Poor, Moderate or Very Good) or disease duration (Long, Short) also vary in either occurrence or type of life events during the past year or occurrence of recent emotional distress. Subjects in Poor control reported more positive and neutral life events during the past year, suggesting even those life changes individuals view benignly may be associated with metabolic control difficulties. Individuals in Poor control also reported more recent symptoms of depression, anxiety and hostility than did individuals in Moderate or Very Good control--symptomatology which may further impair their ability to adhere to a complex self-care regimen. Individuals with Long disease duration reported more positive and negative recent life experiences than did subjects with Short disease duration, but did not evidence concomitant disruptions in metabolic control. The role experience with a chronic disease may play in this finding was unclear, however. Although more research is required to clarify the exact relation of psychosocial variables and diabetic control, these findings suggest that clinically relevant subgroup parameters, subjects' perceptions of life change, and demographic variables may be important factors to assess.     

Osteocalcin 24-hour profiles during normal pregnancy.

The interpretation of previous data on osteocalcin during pregnancy has been complicated by the fact that serum levels, at least in nonpregnant women, display a significant circadian variation. In the present study, serum concentrations of osteocalcin were recorded for 24 h in 12 individual women. In 4 nonpregnant women, there were striking diurnal fluctuations during the sampling period, with values ranging from 0.5 to 4.0 ng/ml. One woman who was investigated in the 11th week of pregnancy showed similar fluctuations in osteocalcin concentrations whereas in the 15th and 17th week values were much lower with minor fluctuations. In 4 women investigated during late pregnancy (weeks 34-38), osteocalcin serum levels were extremely low (range 0.2-0.4 ng/ml), often below the detection limit of the assay, and there was no diurnal variation. Also, in 1 lactating woman, osteocalcin serum levels were low (0.3-0.8 ng/ml) and stable. Low osteocalcin values during pregnancy may indicate a reduced bone turnover possibly mediated via an altered estrogen and growth hormone secretion.     

SCL-25 and recognition of mental disorders reported by primary health care physicians

A marked proportion of primary care patients have mental disorders and problems that remain unrecognized by the patients and their general practitioners. There is furthermore a great variation in the physicians’ ability to detect mental disorders. The aim of the present study was to find out the overall prevalence of mental disorders among patients receiving primary health care. The material consisted of 1000 randomly selected adult patients attending primary care facilities in Turku. The mental disorders were assessed by using the Symptom Checklist (SCL-25) and by general practitioners. According to the SCL-25, one fourth of the sample had a mental disorder. Only two fifths of them could be identified by the general practitioners.     

Infantile autism—fragile X: Molecular findings support genetic heterogeneity

Twenty-two members of 18 families with autism have been examined for the presence of mutations and abnormal methylation in the FMR-1 region at Xq27.3. All patients fulfilled diagnostic criteria of infantile autism. A characteristic pattern of insertion and methylation were detected after Southern blot analysis in 7 autistic individuals expressing the fragile site at Xq27.3. Normal DNA patterns were observed in 15 autistic boys cytogenetically negative for the fragile site. The results indicate a lack of involvement of the FMR-1 region in infantile autists negative for fragile X expression. © 1992 Wiley-Liss, Inc.     

Disposition of oral and intravenous pravastatin in MRP2-deficient TR- rats.

The aim of this study was to characterize the role of the efflux transporter Mrp2 (Abcc2) in the pharmacokinetics of orally and intravenously administered pravastatin in rats. Eight Mrp2-deficient TR- rats and eight wild-type rats were given an oral dose of 20 mg/kg pravastatin. Four TR- animals and four wild-type animals were studied after intravenous administration of pravastatin (5 mg/kg). The TR(-) rats showed a 6.1-fold higher mean area under the plasma concentration-time curve (AUC) of pravastatin (p < 0.001) after oral administration and a 4.7-fold higher AUC (p < 0.01) after intravenous administration of pravastatin as compared with the wild-type animals. The mean systemic (total) clearance of pravastatin was 4.6-fold higher (39.2 versus 8.50 l/h/kg, p < 0.001) and the mean V 4.3-fold higher (14.1 versus 3.29 l/kg, p < 0.01) in the wild-type rats. The mean renal clearance of pravastatin in the TR(-) rats was 16.5-fold increased as compared with the wild-type animals (0.695 versus 0.042 l/h/kg, p < 0.05). The increased systemic exposure to oral pravastatin in the TR- rats was associated with a greater inhibitory effect on 3-hydroxy-3-methylglutaryl CoA reductase, as shown by smaller lathosterol to cholesterol concentration ratios. These results suggest that the reduced biliary pravastatin excretion in the Mrp2-deficient TR- rats is partly compensated for by increased urinary excretion of pravastatin. Furthermore, intestinal Mrp2 does not appear to play a major role in the oral absorption of pravastatin in normal rats.     

Hinweise auf belastungsdeformationen an skelettresten aus prähistorischen brandbestattungen

Zusammenfassung Aus Leichenbränden werden einige Skelettelemente mit Verformungen vorgelegt, die durch äußere Einwirkungen während des Festigkeitsminimums der Knochensubstanz zwischen 400–500°C entstanden sein müssen. Derartige Belastungsdeformationen konnten bisher in einigen Fällen an Gelenkregionen verschiedener Langknochen sowie häufiger an Arcusteilen größerer Wirbel beobachtet werden. Als Ursache wäre eine beabsichtigte Beschwerung der Gelenkregionen zu ihrer Fixierung während der Kremation denkbar sowie aufgrund der an den Corpus vertebrae herangedrückten Arcusteile nur der unterern (!) Wirbel eine Rückenlage des Leichnams auf der Verbrennungsstelle. Experimentelle Verbrennungen, um den erforderlichen Gewichtsdruck zur Erzeugung von Belastungsdeformationen zu ermitteln, wären wünschenswert.     

A school curriculum-based exercise program increases bone mineral accrual and bone size in prepubertal girls: two-year data from the pediatric osteoporosis prevention (POP) study.

This 2-year prospective controlled exercise intervention trial in 99 girls at Tanner stage 1, evaluating a school curriculum-based training program on a population-based level, showed that the annual gain in BMC, aBMD, and bone size was greater in the intervention group than in the controls. INTRODUCTION: Most exercise intervention studies in children, evaluating the accrual of BMD, include volunteers and use specifically designed osteogenic exercise programs. The aim of this study was to evaluate a 2-year general school-based exercise intervention program in a population-based cohort of girls at Tanner stage 1. MATERIALS AND METHODS: Forty-nine girls 7-9 years of age in grades 1 and 2 in one school were included in a school curriculum-based exercise intervention program of general physical activity for 40 minutes per school day (200 minutes/week). Fifty healthy age-matched girls in three neighboring schools, assigned to the general Swedish school curriculum of physical activity (60 minutes/week), served as controls. All girls were premenarchal, remaining in Tanner stage 1 during the study. BMC (g) and areal BMD (aBMD; g/cm2) were measured with DXA of the total body (TB), the lumbar spine (L2-L4 vertebrae), the third lumbar vertebra (L3), the femoral neck (FN), and the leg. Volumetric BMD (vBMD; g/cm3) and bone size were calculated at L3 and FN. Total lean body mass and total fat mass were estimated from the total body scan. Height and weight were also registered. Baseline measurements were performed before the intervention was initiated. Follow-up was done after 2 years. RESULTS: No differences between the groups were found at baseline in age, anthropometrics, or bone parameters. The annual gain in BMC was greater in the intervention group than in the controls: L2-L4, mean 3.8 percentage points (p = 0.007); L3 vertebra, mean 7.2 percentage points (p < 0.001); legs, mean 3.0 percentage points (p = 0.07). The intervention group had a greater annual gain in aBMD: total body, mean 0.6 percentage points (p = 0.006), L2-L4, mean 1.2 percentage points (p = 0.02), L3 vertebra, mean 1.6 percentage points (p = 0.006); legs, mean 1.2 percentage points (p = 0.007). There was also a greater mean annual gain in bone size in the L3 vertebra (mean 1.8 percentage points; p < 0.001) and in the FN (mean 0.3 percentage points; p = 0.02). CONCLUSIONS: A general school-based exercise program for 2 years for 7- to 9-year-old girls (baseline) enhances the accrual of BMC and BMD and increases bone size.