A common approach for ranking of microbiological and chemical hazards in foods based on risk assessment - useful but is it possible?

This article compares and contrasts microbial and chemical risk assessment methodologies in order to evaluate the potential for a common framework for ranking of risk of chemical and microbiological hazards, and developments needed for such a framework. An overview of microbial (MRA) and chemical (CRA) risk assessment is presented and important differences are highlighted. Two microbiological and two chemical hazard-food combinations were ranked based on both a margin of exposure and a risk assessment approach. The comparisons illustrated that it is possible to rank chemical and microbiological hazard-food combinations with traditional approaches from each domain and indicated that the rank order but not the absolute measures is similar using either approach. Including severity in the assessment using DALY reduced differences between hazards and affected the outcome more than which approach was used. Ranking frameworks should include assessment of uncertainty as an integral part of the ranking, and be based on assessment of risk, not safety, and expressed in a common health metric such as disease burden. Necessary simplifications to address data gaps can involve the use of default scenarios. Challenges include comparisons of case-based vs. non-case-based health-endpoints, e.g. biomarker concentration, and integration of the severity of health effects into ranking.

Human umbilical cord blood-derived mesenchymal stromal cells display a novel interaction between P-selectin and galectin-1.

Human multipotent mesenchymal stromal/stem cells (MSCs) have been shown to exert immunomodulatory properties that have great potential in therapies for various inflammatory and autoimmune disorders. However, intravenous delivery of these cells is followed by massive cell entrapment in the lungs and insufficient homing to target tissues or organs. In targeting to tissues, MSCs and other therapeutic cells employ similar mechanisms as leucocytes, including a cascade of rolling and adhesion steps mediated by selectins, integrins and their ligands. However, the mechanisms of MSCs homing are not well understood. We discovered that P-selectin (CD62P) binds to umbilical cord blood (UCB)-derived MSCs independently of the previously known sialyl Lewis x (sLex)-containing ligands such as P-selectin glycoprotein ligand-1 (PSGL-1, CD162). By biochemical assays, we identified galectin-1 as a novel ligand for P-selectin. Galectin-1 has previously been shown to be a key mediator of the immunosuppressive effects of human MSCs. We conclude that this novel interaction is likely to play a major role in the immunomodulatory targeting of human UCB-derived MSCs.

Dietary acrylamide intake and the risk of cancer among Finnish male smokers.

OBJECTIVE: To assess the association between dietary acrylamide intake and the risk of cancer among male smokers. METHODS: The study consisted of 27,111 male smokers, aged 50-69 years, without history of cancer. They were participants of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study in Finland. The men completed a validated dietary questionnaire and a questionnaire on general background characteristics (including smoking habits) at baseline. Incident cases of cancer were identified through the national Finnish Cancer Registry. RESULTS: During an average 10.2 year follow-up, 1,703 lung cancers, 799 prostate cancers, 365 urothelial cancers, 316 colorectal cancers, 224 stomach cancers, 192 pancreatic cancers, 184 renal cell cancers, and 175 lymphomas were diagnosed. Dietary acrylamide intake was positively associated with the risk of lung cancer; relative risk (RR) in the highest versus the lowest quintile in the multivariable-adjusted model was 1.18 ((95% confidence interval (CI) 1.01-1.38, p for trend 0.11). Other cancers were not associated with acrylamide intake. CONCLUSIONS: High acrylamide intake is associated with increased risk of lung cancer but not with other cancers in male smokers.

Sex ratio of newborns: preponderance of males in toxemia of pregnancy.

The ratio of males to females in 1061 babies born to mothers with toxemia of pregnancy is 1.24. The ratio increases as the severity of the disease increases, being 1.71 in cases in which the urinary output of protein is equal to or greater than 3 grams per 24 hours. Histoincompatibility of the fetus and mother, including incompatibility due to an antigen (or antigens) dependent on the Y chromosome, is suggested to function in the pathogenesis of pregnancy toxemia.

Acyl chain-dependent effect of lysophosphatidylcholine on human neutrophils.

Lysophosphatidylcholine (LPC) is the most abundant lysophospholipid in plasma and tissues, and its level increases in ischemia and inflammation. LPC induces various proinflammatory actions in leukocytes, endothelial cells, and smooth muscle cells, but its effects may vary, depending on the acyl chain. In the present study, we identified the molecular species of LPC in human plasma and studied their effects on human neutrophils. Unsaturated LPC species over a wide concentration range (5-200 microM) induced long-lasting superoxide production in neutrophils. The response was preceded by a >10-min lag time and lasted for 60-90 min. Superoxide production was prevented when albumin was added together with LPC at a molar ratio of 1:2 or higher, and significant inhibition was observed even when albumin was added 4-8 min after LPC. Saturation of albumin by fivefold molar excess of stearic acid reduced the inhibitory effect significantly. Saturated LPCs, particularly the most abundant 16:0 species, induced significantly less superoxide production than the unsaturated species and only at 5-10 microM concentrations. Saturated LPC species elicited a several-fold higher increase in cytoplasmic calcium and at >20 microM, increased plasma membrane permeability. A mixture of LPCs mimicking the plasma LPC composition induced nearly similar superoxide production as the most active LPC18:1 alone. These results indicate remarkable acyl chain-dependent differences in the cellular effects of LPC. Elevation of LPC level may increase inflammation through activation of neutrophil NADPH oxidase, particularly when the simultaneous increase of free fatty acids diminishes the ability of albumin to scavenge LPCs.

Consumption of black, green and herbal tea and iron status in French adults.

OBJECTIVE: A number of potential health effects have lately been accorded to tea consumption. It is, however, not clear whether an increase in tea consumption increases the risk of iron depletion in a normal apparently healthy adult population. We have therefore evaluated this. DESIGN: Cross-sectional study. SUBJECTS: A total of 954 men (aged 52-68 years) and 1639 women (aged 42-68 years), who were participants of SU.VI.MAX Study, completed a detailed questionnaire on tea consumption. To determine the iron status of the participants, a venous blood sample was drawn and serum-ferritin was measured. Iron depletion was defined as a serum ferritin concentration <16 microg/l. Three 1-day food records were used to estimate the intake of other dietary enhancing or inhibiting factors of iron absorption, which were included in the logistic regression models. RESULTS: The mean serum-ferritin concentration was not related to black, green and herbal tea consumption in men, pre- or postmenopausal women. Also the risk of iron depletion was in the multivariate model not related to any kind of tea drinking or to the strength of tea, the infusion time or the time of tea drinking. CONCLUSIONS: The data suggest that normal apparently healthy adults are not at risk of iron depletion owing to any kind of tea drinking.

Intake of flavonoids, carotenoids, vitamins C and E, and risk of stroke in male smokers.

BACKGROUND AND PURPOSE: Antioxidants may protect against atherosclerosis and thus prevent cerebrovascular disease. We studied the association between dietary antioxidants and subtypes of stroke. METHODS: The study cohort consisted of 26 593 male smokers, aged 50 to 69 years, without a history of stroke. They were participants of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study in Finland. The men completed a validated dietary questionnaire at baseline. Incident cases were identified through national registers. RESULTS: During a 6.1-year follow-up, 736 cerebral infarctions, 83 subarachnoid hemorrhages, and 95 intracerebral hemorrhages occurred. Neither dietary flavonols and flavones nor vitamin E were associated with risk for stroke. The dietary intake of beta-carotene was inversely associated with the risk for cerebral infarction (relative risk [RR] of highest versus lowest quartile 0.74, 95% CI 0.60 to 0. 91), lutein plus zeaxanthin with risk for subarachnoid hemorrhage (RR 0.47, 95% CI 0.24 to 0.93), and lycopene with risks of cerebral infarction (RR 0.74, 95% CI 0.59 to 0.92) and intracerebral hemorrhage (RR 0.45, 95% CI 0.24 to 0.86). Vitamin C intake was inversely associated with the risk for intracerebral hemorrhage (RR 0.39, 95% CI 0.21 to 0.74). After simultaneous modeling of the antioxidants, a significant association remained only between beta-carotene intake and risk for cerebral infarction (RR 0.77, 95% CI 0.61 to 0.99). CONCLUSIONS: Dietary intake of beta-carotene was inversely associated with the risk for cerebral infarction. No association was detected between other dietary antioxidants and risk for stroke.

Spreading depression induces expression of calcium-independent protein kinase C subspecies in ischaemia-sensitive cortical layers: regulation by N-methyl-D-aspartate receptors and glucocorticoids.

Spreading depression is a wave of sustained depolarization challenging the energy metabolism of the cells without causing irreversible damage. In the ischaemic brain, sreading depression-like depolarization contributes to the evolution of ischaemia to infarction. The depolarization is propagated by activation of N-methyl-D-aspartate receptors, but changes in signal transduction downstream of the receptors are not known. Because protein phosphorylation is a general mechanism whereby most cellular processes are regulated, and inhibition of N-methyl-D-aspartate receptors or protein kinase C is neuroprotective, the expression of protein kinase C subspecies in spreading depression was examined. Cortical treatment with KCl induced an upregulation of protein kinase Cdelta and zeta messenger RNA at 4 and 8 h, whereas protein kinase Calpha, beta, gamma and epsilon did not show significant changes. The gene induction was the strongest in layers 2 and 3, and was followed by an increased number of protein kinase Cdelta-immunoreactive neurons. Protein kinase Cdelta and zeta inductions were inhibited by pretreatment with an N-methyl-D-aspartate receptor antagonist, dizocilpine maleate, which also blocked spreading depression propagation, and with dexamethasone, which acted without blocking the propagation. Quinacrine, a phospholipase A2 inhibitor, reduced only protein kinase C5 induction. In addition, N(G)(-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, did not influence protein kinase Cdelta or zeta induction, whereas 6-nitro-7-sulphamoylbenzo[f]quinoxaline-2,3-dione, an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate/kainate receptor antagonist, and the cyclo-oxygenase inhibitors indomethacin and diclophenac tended to increase gene expression. The data show that cortical spreading depression induces Ca2(+)-independent protein kinase C subspecies delta and zeta, but not Ca(2+)-dependent subspecies, through activation of N-methyl-D-aspartate receptors and phospholipase A2. Even though the signal pathway is similar to the induction described previously in ischaemia for genes implicated in delayed neuronal death, the gene inductions observed here are not necessarily pathogenetic, but may represent a general reaction to metabolic stress.

Alpha-naphthyl acetate esterase activity in human foetal lymphocytes.

Human foetal mononuclear cells from thymus, spleen, liver, bone marrow and peripheral blood at 8-24 weeks of gestation were examined for cytochemical evidence of acid alpha-naphthyl acetate esterase (ANAE) activity. The focal brownish-red ANAE reaction product (T cell staining pattern) was observed in counterstained cytocentrifuged cell smears in the cytoplasm. ANAE-positive lymphoid cells were first observed in the thymus at 9 weeks of gestation. A gradual increase in frequency of ANAE-positive cells in foetal thymus was observed, from about 10% at 14-15 weeks to about 20% at 22-24 weeks of gestation. By 14 weeks of foetal age, spleen and liver contained a few ANAE-positive cells and after 15 weeks of gestation consistent occurrence of ANAE-positive cells was observed in foetal bone marrow and peripheral blood. These results demonstrate that ANAE-positive lymphocytes first appear in the foetal thymus and are subsequently found in the foetal liver, spleen, bone marrow and peripheral blood.

Outcome of thirty patients who underwent repair of posthysterectomy prolapse of the vaginal vault with abdominal sacral colpopexy.

Thirty women experiencing posthysterectomy prolapse of the vaginal vault were treated with abdominal sacral colpopexy between 1984 and 1991. Lyodura (lyophilized cerebral dura mater allograft transplant) was used as the suspensory material in 81 percent and Gore-Tex (reinforced polytetrafluoroethylene) in 16 percent of the operations. There were no perioperative or postoperative complications. At the follow-up examination (mean, three years), good vaginal vault support was observed in 85 percent of the patients. Significant cystocele were seen in 18 percent, and vault prolapse, enterocele, rectocele and chronic perineal laceration each in 15 percent of the patients. At follow-up study, 22 percent of the patients experienced dyspareunia and 41 percent had decreased sexual interest and coital events. Development of stress urinary incontinence in 18 percent of patients was noted. Concomitant Burch colposuspension will cure and prevent stress incontinence and anterior vaginal relaxation. Abdominal sacral colpopexy appears to be a safe and effective method in the treatment of posthysterectomy prolapse of the vaginal vault. In our experience, it seems that coexistent cystocele and rectocele should be corrected in the connection with sacral colpopexy.

The effect of dentinal stimulation on pulp nerve function and pulp morphology in the dog.

The effect of dentinal stimulation on pulpal nerve responses and pulp morphology has been studied in the dog. Canine tooth (n = 25) dentin was stimulated by drilling, probing, and air-blasting for from two to five hours. Acid-etching was used to open dentinal tubules. All test teeth showed disruption of the odontoblast layer and its separation from the predentin; also, dislocation of odontoblast nuclei into dentinal tubules was found in most cases. Single-fiber (n = 14, conduction velocity = 24.3 +/- 7.4 (SD) m/s) recordings of the responses of canine tooth pulpal nerves to dentinal stimulation were made in ten of the stimulated teeth. No changes in the sensitivity of the nerves to dentinal stimulation could be detected. It is concluded that pulpal nerve function and morphological changes of the pulp are not clearly correlated. The condition of the dentin surface seems to be the important factor.

Increasing prevalence of underreporting does not necessarily distort dietary surveys.

OBJECTIVES: To study the magnitude of and trends in energy underreporting and to compare food consumption, nutrient intake and socioeconomic characteristics of underreporters to those of other Finnish adults. DESIGN: Cardiovascular risk factor surveys in 1982 and 1992 using a 3 d food record. Underreporting was defined as energy intake lower than 1.27* BMR, since energy intake < 1.27* BMR is improbable. SETTING: Four areas in Finland, both rural and urban. SUBJECTS: 1746 men and 1921 women, aged, 25-64 y. RESULTS: Proportion of underreporters has increased from 33% in 1982 to 46% in 1992 among women and from 27% in 1982 to 42% in 1992 among men. In a logistic regression model, BMI over 25 kg/m2, female gender, age over 45 y and high educational level predicted underreporting. Shares of energy intake from fat, carbohydrates, protein and alcohol remained the same whether or not underreporters were excluded. However, underreporters consumed significantly higher proportion of vegetables, fish, meat, potatoes, fruit and berries and less fat than others. In the 1992 data the absolute intake of most micronutrients increased and micronutrient densities decreased when underreporters were excluded. CONCLUSIONS: The proportion of underreporters has grown from 1982 to 1992. Results expressed as a percentage of energy intake are not affected by the exclusion of underreporters. In contrast, micronutrient intakes, both absolute and energy density values, were distorted by underreporting. Underreporting should be taken into account in future studies.

Supra-vaginal uterine amputation vs. abdominal hysterectomy: the effects on urinary symptoms with special reference to pollakisuria, nocturia and dysuria.

Post-operative symptoms of hysterectomy have received relatively little attention in the literature. In the present study the first author has personally interviewed and examined 105 abdominal hysterectomy patients and 107 patients with supravaginal uterine amputation pre-operatively and thrice post-operatively. At one year the follow-up percentage was 99.5 (211/212). In the statistical analysis McNemar's test of symmetry and Fisher's exact test were used. Loglinear models were developed where applicable. A number of patients had urinary symptoms pre-operatively: 27.6% of the abdominal hysterectomy and 48.6% of the supra-vaginal amputation patients suffered from pollakisuria; preoperative nocturia and dysuria were present in about 10% of patients in each group. These urinary symptoms disappeared more frequently in patients who underwent supra-vaginal amputation; with regard to pollakisuria the difference is statistically significant. Twelve months post-operatively pollakisuria was present in 10.3% of supra-vaginal amputation and 13.5% of hysterectomy patients. The advantage of supra-vaginal amputation over abdominal hysterectomy with regard to these symptoms may result from the considerably less extensive manipulation of the bladder during supra-vaginal amputation. Possibly the support provided by the remaining stump and the round ligaments fixed to it also help to reduce urinary symptoms in these patients. However, further urodynamic studies are needed.

Superior canal dehiscence: mechanisms of pressure sensitivity in a chinchilla model.

BACKGROUND: Patients with superior canal dehiscence syndrome may experience vertigo and nystagmus when pressure changes occur in the external auditory canal, the middle ear, or the intracranial space. The cause is a defect in the bone of the superior canal. OBJECTIVE: To study the mechanisms of pressure sensitivity of the labyrinth in superior canal dehiscence syndrome and its surgical repair in a chinchilla model. METHODS: We investigated the changes in firing rates of vestibular nerve afferents in the chinchilla in response to changes in external auditory canal pressure before and after fenestration of the superior canal, and after repair of the fenestra. RESULTS: Before superior canal fenestration, external auditory canal pressure changes caused no responses in horizontal canal or otolith afferents, and only 1 of 9 superior canal afferents responded to pressure. After fenestration, all superior canal afferents were excited by positive pressure and inhibited by negative pressure. Half of 18 otolith and most (21 of 33) horizontal canal afferents were unaffected by pressure. The superior canal afferents had higher pressure gain than the horizontal canal afferents (P =.03). Pressure responses could be abolished only by applying a rigid seal to the fenestra. CONCLUSIONS: Fenestration of the superior canal rendered all superior canal afferents sensitive to pressure, whereas less than half of the other afferents became pressure sensitive. The direction of the superior canal afferent responses agreed with the predictions of our model of endolymph flow within the superior canal. A rigid seal applied to the fenestra abolished pressure sensitivity while maintaining physiologic rotational sensitivity.

Premature vertebral endplate ossification and mild disc degeneration in mice after inactivation of one allele belonging to the Col2a1 gene for Type II collagen.

STUDY DESIGN: Skeletal tissues of mice with an inactivated allele of the Col2a1 gene for Type II collagen ("heterozygous knockout") were studied. OBJECTIVE: To determine whether a heterozygous inactivation of the Col2a1 gene has a role in the etiology of spine disorders such as disc degeneration. SUMMARY OF BACKGROUND DATA: Mutations in the COL2A1, COL11A1, COL11A2, and COL9A2 genes have been linked to spine disorders. However, the mechanism by which genetic factors lead to disc degeneration still are largely unknown. METHODS: Spine tissues were studied using radiograph analyses; conventional, quantitative, and polarized light microscopy; immunohistochemistry for the major extracellular components, and in situ hybridization for procollagens alpha1(I) and alpha1(II). Voluntary running activity also was monitored in half of the mice. RESULTS: As the findings showed, 1-month-old heterozygous knockout mice had shorter limb bones, skulls, and spines, as well as thicker and more irregular vertebral endplates, which calcified earlier than in the control mice. They also had a lower concentration of glycosaminoglycans in the anulus fibrosus, in the endplates, and in the vertebral bone than the controls. These features in the heterozygous knockout mice were compensated by the age of 15 months. However, the long bones and skulls of the mature heterozygous mice remained shorter than those of the controls. Gene-deficient mice used the running wheel less. However, physical exercise did not induce any marked structural changes in the skeleton. CONCLUSION: Mice with heterozygous knockout of Col2a1 show subtle early skeletal manifestations that bear some resemblance to those of human spine disorders.

The response of dog intradental nerves to hypertonic solutions of CaCl2 and NaCl, and other stimuli, applied to exposed dentine.

Responses of single nerve units from the canine and incisor pulps of anaesthetized beagles to CaCl2 (3.5 M, 4.9 M and saturated) and NaCl (2.5 M and 4.0 M) were recorded. The sensitivity of these nerve units to drilling and probing of dentine, and to drying with air blasts, was also studied. Twenty-one out of 22 units responded immediately, either with a few spikes or, sometimes, with a 2-5 s train of impulses, to hypertonic CaCl2 when applied to superficial dentine. Deep in dentine, CaCl2 induced immediately responses in 15 out of 21 units. There were responses to hypertonic NaCl in 15 out of 19 units, but only when applied deep in dentine. This firing had a latency of 15-300 s (mean 94 s) and continued until the solution was washed away. Units sensitive to CaCl2 also responded to drilling, probing and drying. When applied to the exposed pulp, CaCl2 never induced nerve activity, but hypertonic NaCl induced responses in all units tested (n = 19); the latencies were 0-300 s (mean 34 s). The mechanism of nerve activation in response to hypertonic CaCl2 is probably hydrodynamic, and common to several other stimuli as in drilling, probing and air drying. Responses to hypertonic NaCl may have been induced by a direct excitatory effect of Na+-ions on the nerve endings or axons in the pulp-dentine border.

The neurophysiological basis and the role of inflammatory reactions in dentine hypersensitivity.

Recent studies indicate that intradental A-type nerve fibres are responsible for the sensitivity of dentine and are activated by fluid movements in dentinal tubules (hydrodynamic mechanism). The patency of the tubules affects dentine sensitivity to a great extent. Both A delta- and A beta-type nerve fibres respond to dentinal (hydrodynamic) stimulation in a similar way. Only a few studies have been made on the regional sensitivity of dentine or the receptive areas of intradental nerve fibres. The results indicate that the fibres innervating different parts of coronal dentine are equally sensitive to dentinal stimulation but those in the cervical area may be less responsive. Inflammation in the pulp can considerably alter dentine sensitivity. In dog teeth with chronically exposed dentine, nerve responses to hydrodynamic stimulation were reduced although other functional changes indicated nerve sensitization. This may be due to spontaneously occurring changes in the exposed dentine that block the tubules. In acute experiments on cat and dog teeth with open dentinal tubules, certain inflammatory mediators increase the sensitivity of the responding nerve fibres. It seems that intradental C-fibres do not respond to hydrodynamic stimulation of dentine. They are polymodal and activated when external stimuli reach the pulp proper. They could perhaps mediate the dull pain connected with pulpitis. However, they might also have an important modifying effect on dentine sensitivity because they can release neuropeptides, which function in the inflammatory reactions.

Activation of intradental nerves in the dog to some stimuli applied to the dentine.

Both scraping of superficial dentine and air blasts induced bursts of action potentials in 19 out of 22 units immediately. In 5 out of 16 units 4.9 mol/l CaCl2-solution was also effective. Dry absorbent cotton activated 5 out of 16 units with a 10-20 s latency. All 18 units tested responded to mechanical irritation of the pulp. Acid etching of dentine made the units more sensitive. Resin impregnation abolished the responses. Drilling of dentine with a turbine bur induced responses of the same type as air blasts. Three units responded to heat and 2 also to cold. Hypertonic NaCl-solution was only effective when applied either to the pulp (in 9 out of 12 units) or to the inner dentine (in 5 out of 17 units). It is concluded that intradental nerve fibres sensitive to several different stimuli exist in the dog. Many of the stimuli used induce fluid flow in dentinal tubules in vitro. Nerve activation might have been due to the same mechanism with all stimuli used, possibly to mechanical distortion of the peripheral pulp tissue as a result of the fluid flow. The findings support the hydrodynamic hypothesis of dentine sensitivity.