Cutaneous Mycobacterium massiliense infection associated with cupping therapy.

Nontuberculous mycobacteria (NTM) are ubiquitous organisms that are now seen as emerging human pathogens. NTM infections are very difficult to diagnose and treat, therefore a high index of clinical suspicion is needed for diagnosis. Cutaneous NTM infections have been primarily reported associated with previous invasive procedures. We report the case of a healthy 59-year-old woman who developed recurring abdominal skin lesions caused by Mycobacterium massiliense after she underwent noninvasive cupping therapy. We identified the pathogen using a PCR assay targeting the erm(41) gene of the bacterium. The patient was treated successfully by en bloc excision and long-term antibiotic treatment. This case shows that cutaneous infection with M. massiliense may occur in an immunocompetent person without an antecedent invasive procedure.

Waning-off effect of serum hepatitis B surface antibody amongst Taiwanese university students: 18 years post-implementation of Taiwan's national hepatitis B vaccination programme.

Hepatitis B virus (HBV) infection and its sequelae remain a major health problem for Taiwan. The national hepatitis B (HB) vaccination programme was first launched in 1984 to combat the spread of this infection. This study examined the status of HBV infection amongst students at a Taiwanese university in 2005, 18 years after the implementation of a nation-wide mass HB vaccination programme. In 2005, 5875 new university entrants, who were born during the period 1 July 1976 to 30 June 1988, were subdivided into one of 12 one-year-interval birth-year cohorts. Each student was individually tested for serum hepatitis B surface antigen (HBsAg), Antibody to hepatitis B surface antigen (anti-HBs) and antibody to hepatitis B core antigen (anti-HBc) status. We observed a declining trend of past exposure to HB infection from 48.7% (1976 birth-year cohort) to 5.2% (1987 birth-year cohort). The prevalence of chronic HB infection also declined from 14.5% (1976 birth-year cohort) to 1.9% (1987 birth-year cohort). The prevalence of persistent HB immunity through (earlier) active vaccination declined from 72% (1984 birth-year cohort) to 41.6% (1987 birth-year cohort). The prevalence of HB infection-naïve individuals increased from 18.2% (1984 birth-year cohort) to 53.1% (1987 birth-year cohort). This study demonstrates that as the implementation of the mass HB vaccination programme in 1984, the incidence of HB infection in Taiwan has declined, although a 'waning-off' effect of serum anti-HBs to low or undetectable levels, which may not provide protection, amongst this student population has arisen, 18 years following the implementation of the nation-wide HB vaccination programme. Such a situation may mean that these individuals may not be effectively protected against future HB infection. A booster dose of HB vaccine, given 18 years following HB vaccination, perhaps even earlier, should be considered.

Interferon regulatory factor-1-induced apoptosis mediated by a ligand-independent fas-associated death domain pathway in breast cancer cells.

Interferon (IFN) regulatory factor-1 (IRF-1) is a transcription factor that has apoptotic anti-tumor activity. In breast cancer cell types, IRF-1 is implicated in mediating apoptosis by both novel and established anti-tumor agents, including the anti-estrogens tamoxifen and faslodex. Here we demonstrate that in MDA468 breast cancer cells, apoptosis by IFN-gamma is mediated by IRF-1 and IFN-gamma, and IRF-1-induced apoptosis is caspase-mediated. IRF-1 induction results in cleavage of caspase-8, -3 and -7, and application of caspase inhibitors attenuate activated cleavage products. IRF-1-induced apoptosis involves caspase-8 since apoptosis is significantly decreased by the caspase-8-specific inhibitor IETD, c-FLIP expression and in caspase-8-deficient cancer cells. Furthermore, we demonstrate that IRF-1-induced apoptosis requires fas-associated death domain (FADD) since dominant-negative FADD expressing cells resist IRF-1-induced apoptosis and activated downstream products. Immunofluorescent studies demonstrate perinuclear colocalization of FADD and caspase-8. Despite the known role of FADD in mediating death-ligand induced apoptosis, neutralizing antibodies against classical death receptors do not inhibit IRF-1 induced apoptosis, and no secreted ligand appears to be involved since MDA468 coincubated with IRF-1 transfected cells do not apoptose. Therefore, we demonstrate that IRF-1 induces a ligand-independent FADD/caspase-8-mediated apoptosis in breast cancer cells.

Effects of extremely low frequency magnetic fields on pain thresholds in mice: roles of melatonin and opioids.

1. We studied the effects of extremely low frequency (ELF, 60 Hz) magnetic fields (MFs) on pain thresholds using the hot plate test. The implication of opioid and benzodiazepine system in the MFs-induced alteration of pain thresholds was also studied. 2. There was an increase at night time and a decrease at daytime of pain thresholds in normal mice. Exposure of MFs (24 h, 20 gauss (G)) inhibited the increase of pain thresholds at night time and even produced hyperalgesia at daytime. 3. The increase of pain thresholds induced by melatonin at daytime was inhibited by exposure to MFs (24 h, 20 G) or opioid antagonist naloxone. The MFs and naloxone synergically inhibited hypoalgesia produced by melatonin. The hyperalgesia at daytime after MFs exposure was potentiated by the benzodiazepine agonist, diazepam, and inhibited by the benzodiazepine antagonist, flumazenil. There was no significant difference in all rotarod performance we tested. 4. From these results, it is suggested that exposure to MFs inhibits the increase of pain thresholds at night time and produces hyperalgesia at daytime with the involvement of opioid and benzodiazepine systems.

Effects of inhalational anesthetics on alpha2-adrenergic signaling in isolated platelets.

(1) The hypothesis that inhalational anesthetics affect G-protein linked alpha2 adrenergic signaling pathway was investigated using human platelets as a model system. (2) Alpha2 receptor stimulation by UK-14304, a potent and selective agonist, inhibits cAMP production induced by prostaglandin I2 (PGI2). (3) Brief stimulation (30 s) with PGI2 raised cAMP levels in platelets by 25-fold; UK-14304 suppressed the PGI2 stimulus by 80%. (4) Halothane at fractional minimum alveolar concentration (MAC) through super physiological levels (16 MAC) had no effect on basal or prostacyclin stimulated levels of cAMP, nor did it have any effect on the inhibition of cAMP production by UK-14304. Moreover, isoflurane, enflurane and sevoflurane had no significant effect on cAMP production at 1.5 or 8 MAC. The results suggest alpha2 and PGI2 signaling pathways are not sensitive to volatile anesthetics including the alpha2 or PGI2 receptor/G-protein complex, G-protein/adenylyl cyclase complex and adenylyl cyclase itself. (5) The possibility that halothane and related anesthetics act more distally in the pathway, on cAMP-dependent protein kinase (PKA), was investigated by measuring the phosphorylation pattern of endogenous platelet proteins by PKA. (6) An increase in the [32P]phosphate incorporation was observed in platelets exposed to either, low doses of PGI2 or isobutylmethylxanthine (IBMX). Halothane, isoflurane, enflurane or sevoflurane further increased the level of [32P]-incorporation. The apparent increase in PKA activity suggests that at least in platelets, volatile anesthetics activate PKA-dependent pathways which should antagonize alpha2 adrenergic signaling.