Primary cultures of rat astrocytes respond to thiamine deficiency-induced swelling by downregulating aquaporin-4 levels

Imaging studies indicate that cerebral edema is an important consequence of Wernicke's encephalopathy (WE), a disorder caused by thiamine deficiency (TD). We have investigated this problem using a recently developed in vitro astrocyte model of TD. Measurement of cell volume using the 3-O-methylglucose uptake method revealed a dose-dependent swelling of astrocytes during exposure to TD conditions. Time course studies indicated a progressive volume increase up to a maximum of 93% above controls after 4 days of treatment. This swelling then partially resolved, and remained stable for up to 10 days following commencement of TD treatment. Measurement of aquaporin-4 (AQP-4) levels showed a 44% loss after 10 days and a temporal profile consistent with an important role for this water channel protein in astrocyte cell volume changes during TD. Our findings of astrocyte swelling in TD are consistent with previous reports of focal brain edema in cases of WE, and indicate that AQP-4 may be an important target for ameliorating some of the clinical problems associated with this disorder.     

Epidemiology and morbidity of Schistosoma mansoni infection in a fishing community along Lake Albert in Uganda

Schistosoma mansoni infection, associated morbidity and symptoms were studied in Piida fishing community at Butiaba, along Lake Albert, Uganda, from November 1996 to January 1997. The study revealed that S. mansoni is highly endemic with an overall prevalence of 72%, a mean intensity of 419.4 eggs per gram (epg) faeces (geometric mean for positives only), with 37.8% of males and 33.0% of females excreting over 1000 epg. Prevalence and intensity peaked in the 10-14 year old age group and decreased with increasing age. Females were less heavily infected than males. Differences were also shown between tribes. Diarrhoea and abdominal pain were commonly reported in Piida. However, no clear-cut correlation between intensity of S. mansoni infection and these conditions could be demonstrated, indicating that retrospective questionnaires concerning S. mansoni related-symptomatology are of limited value. Organomegaly, as assessed by ultrasonography, was frequent and hepatomegaly was associated with heavy S. mansoni infection. No correlation was demonstrated between splenomegaly and infection. This study emphasizes that schistosomiasis mansoni is a major public health problem in Piida fishing community and presumably also in many similar fishing communities. These observations call for immediate intervention and can help in planning long-term strategies for sustainable morbidity control.     

A population survey found an association between self-reports of traumatic brain injury and increased psychiatric symptoms

OBJECTIVE: This study determined whether self-reported Traumatic Brain Injury (TBI), identified in a community sample and occurring up to 60 years previously, is associated with current psychiatric symptoms, suicidality, and psychologic well-being. STUDY DESIGN AND SETTING: Three age cohorts (20-24, 40-44, 60-64) were randomly sampled from the cities of Canberra and Queanbeyan, Australia, yielding a total of 7,485 participants. The samples were administered scales measuring anxiety, depression, suicidality, positive and negative affect, personality traits, and physical health status. RESULTS: Of the total sample, 5.7% reported history of TBI involving loss of consciousness for at least 15 min, occurring an average of 22 years previously. History of TBI was associated with increased symptoms of depression, anxiety, negative affect, and suicidal ideation. CONCLUSION: History of TBI is a risk factor for psychiatric morbidity. The effect is greatest in young adults, and occurs up to several decades subsequent to the occurrence of TBI.     

The treatment of postnatal depression by health visitors: impact of brief training on skills and clinical practice

BACKGROUND: Postnatal depression can be effectively treated by cognitive behavioural counselling (CBC), a simple intervention designed to be delivered by non-specialists in mental health. METHODS: Health visitors were trained in CBC and post-training changes in counselling skills, clinical practice and costs were assessed. RESULTS: Following training health visitors showed improved counselling skills, and they carried out more mental health assessments, recorded mental symptoms more often and treated more women themselves. However, their mean number of contacts with depressed women did not change; and the number of urgent contacts diminished. Referrals to general practitioners did not increase but there was an increase in referrals to mental health services. Costs to health visitor practice did not increase. LIMITATIONS: Assessment of clinical practice was based on health visitor records. The study uses a 'before and after' design rather than randomisation of subjects. CONCLUSIONS: Training health visitors in CBC leads to improved counselling skills and corresponding changes in clinical practice, without increasing the costs of health visitor practice.     

Why semantic dementia drives you to the dogs (but not to the horses): A theoretical account

This paper describes a patient (IH) with semantic dementia and severe impairment in all semantic categories except for numerical knowledge, which was preserved. IH showed a severe deficit in reading and writing non-number words (e.g., candle, juice) and nonwords, and preservation of reading and writing number words (e.g., one, forty) and numerals (e.g., 1, 40). IH's pattern of performance can be explained by the combination of a selective sparing of one semantic category--i.e., numbers--with a total deficit of nonsemantic processes for mapping letters and sounds. As number was the only spared semantic category in the presence of these other nonsemantic deficits, it follows that the semantic route is sufficient for accurate reading and spelling. Our data clarify the nature of reading and writing processes and support the functional and neuroanatomical independence of the number domain.     

Bacterial adhesion to titanium-oxy-nitride (TiNOX) coatings with different resistivities: a novel approach for the development of biomaterials

In this study the quantitative adhesion of a strain of Staphylococcus epidermidis, Streptococcus mutans and Pseudomonas aeruginosa to and the ease of removal from different TiNOX coatings was investigated by means of a parallel plate flow chamber and in situ image analysis. Quality of adhesion was determined by counting bacteria which remained attached to the surface after exposure to an air-liquid interface. S. epidermidis and S. mutans showed a bipolar adhesion pattern with highest numbers of adhesion at low and high resistivity with lowest adhesions at a resistivity of 10(4) microohms cm. P. aeruginosa was the least adherent organism. These results indicate that the affinity of these three strains under the current experimental conditions is minimal for TiNOX coatings with a specific resistivity. TiNOX coatings with pre-adsorbed fibrinogen showed different numbers of S. epidermidis adhered to the different coatings. However, the affinity of this strain for fibrinogen-coated TiNOX remains low when the resistivity is around 10(4) microohms cm. This indicates that the specific influence of the resistivities of the TiNOX coatings is transferred through the adsorbed fibrinogen film to the interface with adhering bacteria.     

Response of alveolar macrophages from inducible nitric oxide synthase knockout or wild-type mice to an in vitro lipopolysaccharide or silica exposure

The role of nitric oxide (NO) in pulmonary disease has been controversial with both antiinflammatory (scavenging radicals and inhibiting NF-êB activation) and proinflammatory (forming highly reactive peroxynitrite and augmenting NF-êB activation by inflammatory agents) actions reported. Therefore, a study has been initiated to determine whether deletion of the inducible nitric oxide synthase (iNOS) gene in the C57BL/6J mouse alters the pulmonary macrophage response to lipopolysaccharide (LPS) or silica. The objective of the initial phase of this study was to determine the difference in responsiveness of alveolar macrophages (AMs), harvested from naive wild-type (WT) or iNOS knockout (iNOS KO) mice, to an in vitro LPS or silica exposure. Primary AMs were obtained by bronchoalveolar lavage (BAL) from age- and weight-matched iNOS KO and WT mice. The cells were treated with interferon-gamma (IFN-?) (50 U/ml), IFN-? (50 U/ml) + LPS (1 microg/ml), LPS (0.01-100 microg/ml), or silica (25-250 microg/ml). The following parameters were measured: nitrate and nitrite (NOx), tumor necrosis factor-á (TNF-á), macrophage inflammatory protein-2 (MIP-2), intracellular generation of the reactive oxygen species (ROS) hydrogen peroxide (H(2)O(2) and superoxide (O(*-2)), and basal (unstimulated) total antioxidant capacity. Data show a significant increase in NOx production upon exposure to IFN-? +/- LPS in the WT but not iNOS KO AMs. NOx production by iNOS KO or WT AMs was not altered by in vitro exposure to LPS or silica alone. LPS, but not silica, induced TNF-á and MIP-2 production in both iNOS KO and WT AMs. Statistical analysis of concentration response curves found a significant tendency for greater mediator production in the iNOS KO versus WT AMs. Basal intracellular production of H(2)O(2) and O(*- 2) was significantly greater in the iNOS KO compared to WT AMs. In contrast, LPS- (10 microg/ml) or silica- (100 microg/ml) stimulated intracellular oxidant production was lower in iNOS KO AMs, but overall (basal + stimulated) inflammatory capacity was similar between the cell types. The basal total antioxidant production of the iNOS KO AMs was approximately twofold higher than the WT AMs. In conclusion, certain compensatory changes appear to occur in AMs from iNOS KO mice. In response to the inability to induce NO production, iNOS KO AMs exhibit significantly higher basal generation of H(2)O(2) and (O(*- 2)) as well as higher total antioxidant levels. In addition, LPS induced TNF-á and MIP-2 production tend to be higher in AMs from iNOS KO mice. Such compensatory changes in the AM response may affect the response of iNOS KO mice to inflammatory exposures.     

Men are more susceptible than women to direct pressure on unmyelinated ulnar nerve fibers

Ulnar nerve injury, the most common form of perioperative peripheral nerve injury, has a 3:1 male/female predominance. Neither the mechanism of perioperative ulnar nerve injury nor the reasons for the increased male susceptibility are well understood. We used an experimental model with arm flexion at the elbow, direct pressure on the ulnar nerve, and arm ischemia as distinct stress mechanisms to induce adverse changes in ulnar current perception thresholds (CPTs) on 3 groups of 40 male and 40 female volunteers (a total of 240 volunteers). CPT measurements were repeated at 2000-, 250-, and 5-Hz stimulating frequencies, specific to A-beta, A-delta, and unmyelinated C-fibers, respectively. Ischemia produced significant increases in CPT with all three stimulating frequencies, and there were no detectable differences between men and women. Flexion failed to produce significant CPT increases at any of the three stimulating frequencies, with no sex-based differences. Direct pressure produced significant CPT increases at 5 and 250 Hz, indicating inhibition of both unmyelinated C-fibers and myelinated A-delta fibers. C-fibers, but not A-delta fibers, demonstrated sex differences with direct pressure; there was a 1.7-fold (95% confidence interval, 1.2- to 2.4-fold) greater effect in men. Ischemia significantly inhibited the function of all three fiber types, perhaps sufficient to overwhelm gender differences. IMPLICATIONS: The ability of direct pressure to produce a greater inhibition of unmyelinated C-fibers in male subjects compared with female subjects is consistent with, and may help explain, the male increased susceptibility to perioperative ulnar nerve dysfunction.     

Pathogen inactivation of RBCs: PEN110 reproductive toxicology studies

BACKGROUND: The novel PEN110 chemistry (INACTINE, V.I. Technologies) process for the purification of blood for transfusions involves treating WBC-reduced RBCs with PEN110 to inactivate a wide spectrum of pathogens. The washed RBC preparation has a residual PEN110 level of less than 0.00005 mg per mL. It is important to verify that the trace amounts of residual PEN110 in blood prepared for transfusions will not produce adverse effects on reproduction, fertility, or fetal development. STUDY DESIGN AND METHODS: A fertility and early embryonic development study was conducted in male and female Sprague-Dawley rats at IV doses of up to 0.5 mg PEN110 per kg of body weight following standard regulatory protocols. A fetal developmental study was conducted in Hra:(NZW)SPF pregnant rabbits at IV doses of up to 1.0 mg per kg of body weight following standard regulatory protocols. In both cases the highest dose was shown to be a maximum tolerated dose in pregnant animals based on body weight gain during pregnancy. RESULTS: In the fertility and early embryonic development study, no treatment-related effects were noted on estrous cycles, pregnancy rate, implantation sites, corpora lutea, number of resorptions, and live embryos in female rats or sperm motility, sperm morphology, and sperm counts in male rats. In the fetal developmental study, PEN110 had no effect on embryofetal viability and growth. This is consistent with other data indicating that PEN110 is rapidly cleared by urinary excretion. On a mg per kg of body weight dose basis, the no-observed-effect level doses for rats in the fertility study and rabbits in the developmental study were 2,000 and 4,000 (320 and 1,300 scaled to dose per unit body surface area [DBSA]) times that which a person would receive given 1 unit of treated blood. Considering the cumulative animal dosages, the safety factor values increase to 48,000- and 60,000-fold (7,700 and 19,400 scaled to dose per unit body surface area). CONCLUSION: These results indicate that the trace amount of residual PEN110 in the purified blood component is well below the level that could present a risk of reproductive toxicity to the patient.