S-Adenosylmethionine (SAMe) attenuates acetaminophen hepatotoxicity in C57BL/6 mice

Hepatic toxicity is associated with excessive dosages of the over the counter analgesic, acetaminophen (APAP). The aim of this study was to explore protection by the nutritional agent S-adenosylmethionine (SAMe) on APAP hepatotoxicity. Male C57BL/6 mice were injected intraperitoneal (i.p.) with 500 mg/kg (15 ml/kg) APAP or water vehicle (VEH). SAMe was injected i.p. at a dose of either 1000 mg/kg (5 ml/kg) just prior or 500 mg/kg SAMe 15 min prior to administration of VEH or APAP. Comparison of groups showed that SAMe reduced APAP toxicity. Plasma alanine aminotransferase (ALT) levels were increased 2 and 4 h after APAP administration when compared to vehicle (VEH) controls. Liver weight was increased relative to the VEH group within 4 h after APAP treatment. Histological examination by light microscopy confirmed small changes in morphology within 2 h after APAP injection and marked centrilobular necrosis within 4 h in the APAP group. In contrast, when APAP was administered to SAMe pretreated mice, ALT and liver weights were comparable to the VEH and SAMe groups. Histological examination also showed that SAMe produced a marked protection in APAP mediated centrilobular necrosis at 4 h after APAP injection. APAP administration depressed hepatic glutathione levels when monitored at 2 and 4 h. Lipid peroxidation was induced above VEH values 2 and 4 h after APAP injection. Consistent with the SAMe protection of APAP hepatic toxicity, the expected depletion of hepatic glutathione (GSH) levels by APAP was prevented by SAMe pretreatment. SAMe pretreatment also prevented the induction of lipid peroxidation at 2 and 4 h post-APAP administration. In conclusion, SAMe provides protection from APAP hepatic toxicity at 2 and 4 h post-APAP injection. SAMe pretreatment prevented APAP associated depletion in hepatic glutathione and induction of lipid peroxidation as part of its mechanism of protection.     

The impact of changing dental needs on cost savings from fluoridation

Background:  Although community water fluoridation has been one of the cornerstone strategies for the prevention and control of dental caries, questions are still raised regarding its cost-effectiveness. This study assessed the impact of changing dental needs on the cost savings from community water fluoridation in Australia.
Methods:  Net costs were estimated as Costs_(programme) minus Costs_{(averted caries).} Averted costs were estimated as the product of caries increment in non-fluoridated community, effectiveness of fluoridation and the cost of a carious surface. Modelling considered four age-cohorts: 6–20, 21–45, 46–65 and 66+ years and three time points 1970s, 1980s, and 1990s. Cost of a carious surface was estimated by conventional and complex methods. Real discount rates (4, 7 (base) and 10%) were utilized.
Results:  With base-case assumptions, the average annual cost savings/person, using Australian dollars at the 2005 level, ranged from $56.41 (1970s) to $17.75 (1990s) (conventional method) and from $249.45 (1970s) to $69.86 (1990s) (complex method). Under worst-case assumptions fluoridation remained cost-effective with cost savings ranging from $24.15 (1970s) to $3.87 (1990s) (conventional method) and $107.85 (1970s) and $24.53 (1990s) (complex method). For 66+ years cohort (1990s) fluoridation did not show a cost saving, but costs/person were marginal.
Conclusions:  Community water fluoridation remains a cost-effective preventive measure in Australia.     

Acute spinal cord injury: MR imaging at 1.5 T

Thirty-seven magnetic resonance (MR) imaging studies were performed with a 1.5-T magnet and surface coils in 27 patients with suspected spinal cord injuries. Imaging was performed 1 day to 6 weeks after injury. Cord abnormalities were seen with MR in 19 patients, while skeletal and/or ligamentous injuries were seen in 21 (78%). Three types of MR signal patterns were seen in association with cord injuries. Acute intraspinal hemorrhage was seen in five patients with cord injuries and demonstrated decreased signal intensity on T2-weighted images obtained within 24 hours of injury. Cord edema and contusion had high signal intensity on T2-weighted images and were observed in 12 cases with cord injury. Neurologic recovery, determined in 16 patients, was insignificant in patients with intraspinal hemorrhage; however, patients with cord edema or contusion recovered significant neurologic function. MR at 1.5 T is extremely useful in the diagnosis of acute cord injury and also demonstrates potential in predicting neurologic recovery.     

Growth rate as a prognostic factor in localized invasive cutaneous melanoma

Background Melanoma is a tumour with a very variable progression. Whilst some melanomas grow slowly over many years, others can reach several millimetres in thickness in just a few weeks. Since melanoma is a visible superficial tumour, the information obtained from the clinical interview may be of use to calculate the speed of growth of the melanoma. Objective This study aims to assess the growth rate (GR) of melanomas and the association of this GR with various clinical and pathological factors and their usefulness as prognostic markers for localized invasive cutaneous melanomas. Methods The GR of melanomas was calculated as the ratio of tumour thickness to time of development, as obtained from the clinical history (in millimetres per month). Results Applying the GR calculation to patients with a localized melanoma showed a significant association between melanomas with a GR greater than 0.4 mm per month and an age of 65 years or over, male sex, nodular melanoma, tumour thickness, level of invasion, the presence of ulceration and a high mitotic index. As an independent prognostic factor for overall survival, the GR proved to be significant (P = 0.024). Conclusion The GR of localized cutaneous melanomas may be a possible prognostic factor for survival. Additionally, rapid GR is associated with male patients more advanced in age at diagnosis, which suggests the need to assess new strategies for the early detection of these melanomas.     

Dermatitis artefacta of the breast: a retrospective analysis of 27 patients (1976–2006)

Background Dermatitis artefacta (DA) is defined as all dermatological, self‐inflicted skin lesions, where the patient denies having produced the lesions. Objectives The purpose of this study is to make a single‐centre retrospective clinical review of patients diagnosed as DA of the breast. Materials and methods During a 30‐year period (1976–2006), patients diagnosed as DA of the breast, seen in the Department of Dermatology of the Virgen Macarena Hospital in Seville, were recorded. Clinical and epidemiological features are described. Results A total of 27 women with a mean age of 34.33 years were selected representing 13.43% of the total of DA patients recorded (n = 201) in this period. The most frequent clinical forms were: excoriations (nine patients, 33.33%) and ulcers (nine patients, 33.33%), followed by burns (six patients, 22.22%), blisters (one patient, 3.70%), contact dermatitis (one patient, 3.70%) and haematomas (one patient, 3.70%). Ten of the cases were located exclusively on the breasts, whereas 17 had also other locations such as face in seven cases, arms in five cases, abdomen in five cases and the entire body in two cases. Cutaneous lesions were treated with occlusive bandages using zinc paste or plaster splint when necessary. Conclusion To our knowledge, this is the major series of DA of the breast studied. This complicated psychodermatological condition requires a correct diagnosis, appropriate management and psychiatric assessment.     

Oxygen consumption during sleep in atopic dermatitis

Measurements of oxygen consumption (VO2) were made during sleep in 10 patients with atopic dermatitis. Two groups of healthy children acted as controls. All subjects were studied in bed in an environmental temperature of 24-26 degrees C, and sleep was confirmed during continuous electroencephalographic monitoring. Mean (SD) values of VO2 in sleeping patients who were not scratching ranged from 4.0 (0.4) to 7.4 (0.7), which was not statistically significantly different from control values which ranged from 3.24 (0.3) to 5.56 (0.4). During scratching (while asleep), which occurred in nine out of 10 patients with atopic dermatitis, the mean values of VO2 ranged from 4.5 (0.04) to 10.4 (2.7), and this was significantly higher than the non-scratching patients and the control values. Scratching during sleep in children with atopic dermatitis is associated with increased VO2.     

Organization, expression and polymorphism of the human persyn gene

Persyn is a recently identified member of the synuclein family with a distinct pattern of expression during pre- and postnatal development of the mouse peripheral and central nervous systems. As with other synucleins, persyn is believed to be involved in the pathogenesis of human neurodegenerative diseases. However, in contrast to other synucleins, high levels of persyn mRNA expression were also found in advanced breast carcinomas, suggesting an involvement of the encoded protein in breast tumour progression. Here we have used an antibody specific to human persyn to demonstrate that the level of this protein is increased in ageing cerebral cortex and in breast tumours. We cloned, characterized and sequenced the human persyn genomic locus and localized it to the long arm of chromosome 10 in the q23.2-q23.3 region. Sequence information was used to search for specific mutations in the protein coding regions of persyn mRNA and the persyn gene in breast tumours and tumour cell lines. No tumour-specific mutations were found, but two linked polymorphisms in the coding region were detected, both in mRNA and exons III and IV of the gene. These results suggest that development of breast tumours correlates with overexpression of the wild-type persyn protein. Detailed characterization of the human persyn locus is important for further studies of the involvement of persyn in neurodegeneration and malignancy.      

Dental caries experience in young Australian Army recruits 2008

Background: Recent studies have shown a substantial decline in caries experience in Australian Army recruits between 1996 and 2002–2003, and in Australian adults between 1987–1988 and 2004–2006. However, studies in children have reported an increasing trend in caries experience between 1998 and 2002. The aim of this study was to investigate caries experience in Australian Army recruits in 2008. Methods: A cross‐sectional study involving 1084 Australian Army recruits was conducted from January to May 2008. Data were obtained from a clinical dental examination with bitewing radiographs, and a questionnaire elicited socio‐demographic data and history on lifetime exposure to fluoridated drinking water. Results: Mean DMFT scores were 3.16, 4.08, 5.16 and 7.11 for recruits aged 17–20, 21–25, 26–30 and 31–35 years, respectively. Recruits with a lifetime exposure to fluoridated drinking water had a mean DMFT of 3.02, while recruits with no exposure had a mean DMFT of 3.87. Conclusions: Caries experience in Australian Army recruits aged 17–25 years increased between 2002–2003 and 2008. Recruits with lifetime exposure to fluoridated drinking water had 25 per cent less caries experience compared with recruits who had no exposure to fluoridated drinking water after adjusting for the effects of age, gender, education and socio‐economic status.     

Patterns of chloroform-induced regenerative cell proliferation in BDF1 mice correlate with organ specificity and dose-response of tumor formation

It has been reported that chloroform administered to BDF1 mice by inhalation for 2 years at concentrations of 5, 30 or 90 p.p.m. for 6 h/day, 5 days/week induced an increase in renal cell tumors in male but not female mice exposed to the doses of 30 and 90 p.p.m. A small increase in liver tumors was statistically significant in the female mice at 90 p.p.m. if the incidences of carcinomas and adenomas were combined. Because chloroform is not a DNA reactive mutagen, a 13-week time-course and dose-response study was conducted under conditions of the original bioassay to examine whether regenerative cell proliferation was an underlying mechanism of carcinogenesis. Mice were given bromodeoxyuridine via infusion during the last 3.5 days prior to necropsy to label cells in S-phase. Chloroform induced pathology and regenerative cell proliferation, measured as the labeling index (LI, percentage of cells in S-phase), were assessed microscopically and immunohistochemically. Male mice exposed to 30 and 90 p.p.m. exhibited a dose-dependent increase in regenerating tubules within the renal cortex and up to a 31-fold increase in LI. No renal lesions or increased LI were observed in females. Increased centrilobular to midzonal hepatocyte degeneration and vacuolation and a 7-fold increase over controls in the hepatocyte LI were observed in the female mice at 90 p.p.m. at 13 weeks. Males exhibited similar pathology, but the increase in LI was not sustained. The observed correlations between cytolethality and regenerative cell proliferation with tumor formation supports extensive evidence that chloroform induces cancer via a non- genotoxic-cytotoxic mode of action. A concentration of 5 p.p.m. is the no-observed-adverse-effect level for nephrotoxicity, cell proliferation and cancer. An appropriate safety factor applied to this value is a straightforward approach to cancer risk assessment that is consistent with the mode of action of chloroform.