The emergence of drug-resistant Streptococcus pneumoniae and host risk factors for carriage of drug-resistant genes in northeastern Japan

Our 2-year study includes research into the occurrence, molecular characteristics, and host risk factors for the carriage of drug-resistant strains of Streptococcus pneumoniae as a continuation of our previous report. From September 2001 to June 2003, strains of S. pneumoniae were isolated from the nasopharynx of children with respiratory tract infection in Soma General Hospital. Of the total of 949 strains, 761 (81%) had a decreased susceptibility to penicillin (MIC > 0.12 microg/ml), while 818 (86%) were resistant to erythromycin (MIC > 1 microg/ml) and 789 (83%) were resistant to clarithromycin (MIC > 1 microg/ml). More than half of the strains had decreased susceptibility to meropenem. Gene analysis of 226 randomly selected strains showed that 200 strains (88.5%) had one or more altered pbp genes and 191 strains (84.5%) had mef(A) and/or erm(B) genes. We reviewed the patient backgrounds for previous antibiotic use, age, daycare attendance, and siblings. Previous use of oral beta-lactams has shown a strong relationship with the carriage of altered pbp genes (P value < 0.01), and previous oral macrolide use has been related to the carriage of macrolide-resistant genes (P value < 0.01). The controlled use of antibiotics might be an important factor in preventing the emergence of S. pneumoniae with antibiotic-resistant genes.     

ORL1 receptor-mediated down-regulation of mPER2 in the suprachiasmatic nucleus accelerates re-entrainment of the circadian clock following a shift in the environmental light/dark cycle

The circadian pacemaker in the suprachiasmatic nucleus (SCN) generates the near 24-h period of the circadian rhythm and is entrained to the 24-h daily cycle by periodic environmental signals, such as the light/dark cycle (photic signal), and can be modulated by various drugs (non-photic signals). The mechanisms by which non-photic signals modulate the circadian clock are not well understood in mice. In mice, many reportedly non-photic stimuli have little effect on the circadian rhythm in vivo. Herein, we investigated the molecular mechanism in W-212393-induced phase advance using mice. W-212393 caused a significant phase advance of locomotor activity rhythm in mice at subjective day. Injection of W-212393 during subjective day elicited down-regulation of mPER2 protein in the SCN shell region, but not mPer2 mRNA. Administration of W-212393 during subjective day failed to produce phase advance in mPer2-mutant mice as well as in ORL1 receptor deficient mice. Furthermore, we show that such inhibition of mPER2 accelerates re-entrainment of the circadian clock following an abrupt shift in the environmental light/dark cycle, such as occurs with transmeridian flight. The present results suggest that post-translational down-regulation of mPER2 protein in the shell region of mouse SCN may be involved in W-212393-induced non-photic phase advance.     

Repeated treatment with cannabidiol but not Delta9-tetrahydrocannabinol has a neuroprotective effect without the development of tolerance

Both Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and cannabidiol are known to have a neuroprotective effect against cerebral ischemia. We examined whether repeated treatment with both drugs led to tolerance of their neuroprotective effects in mice subjected to 4h-middle cerebral artery (MCA) occlusion. The neuroprotective effect of Delta(9)-THC but not cannabidiol was inhibited by SR141716, cannabinoid CB(1) receptor antagonist. Fourteen-day repeated treatment with Delta(9)-THC, but not cannabidiol, led to tolerance of the neuroprotective and hypothermic effects. In addition, repeated treatment with Delta(9)-THC reversed the increase in cerebral blood flow (CBF), while cannabidiol did not reverse that effect. Repeated treatment with Delta(9)-THC caused CB(1) receptor desensitization and down-regulation in MCA occluded mice. On the contrary, cannabidiol did not influence these effects. Moreover, the neuroprotective effect and an increase in CBF induced by repeated treatment with cannabidiol were in part inhibited by WAY100135, serotonin 5-HT(1A) receptor antagonist. Cannabidiol exhibited stronger antioxidative power than Delta(9)-THC in an in vitro study using the 1,1-diphenyl-2-picryhydrazyl (DPPH) radical. Thus, cannabidiol is a potent antioxidant agent without developing tolerance to its neuroprotective effect, acting through a CB(1) receptor-independent mechanism. It is to be hoped that cannabidiol will have a palliative action and open new therapeutic possibilities for treating cerebrovascular disorders.     

Exocytosis of D-aspartate from INS-1E clonal beta cells

D-Aspartate is present in the central nervous system and various endocrine organs, and modulates their neuroendocrine function. In islets of Langerhans, alpha and beta cells contain D-aspartate. Here we show that INS-1E clonal beta cells contain the highest amount of D-aspartate. Immunohistochemical analysis with specific antibodies against D-aspartate indicated that D-aspartate is co-localized with insulin. Upon the addition of K(+), both D-aspartate and insulin are secreted from the cells in a Ca(2+)-dependent manner. A Ca(2+) ionophore, A23187, also triggers the release of D-aspartate and insulin in the presence of Ca(2+). Bafilomycin A(1), a specific inhibitor of V-ATPase and V-ATPase-linked secondary transport, inhibits the secretion of D-aspartate. These results support the idea that D-aspartate is present in insulin-containing secretory granules and co-secreted with insulin through exocytosis.     

Case of a ruptured vertebral artery dissecting aneurysm recanalized after internal trapping

A 35-year-old male experienced a sudden onset of severe headache. A CT scan revealed subarachnoid hemorrhage. By cerebral angiography, he was diagnosed as having a ruptured right vertebral artery dissecting aneurysm (VADA). It was successfully treated by endovascular occlusion of the affected site, including the aneurysm and parent artery, by using detachable coils. A follow-up angiography obtained seven months after the first treatment revealed the recanalization of the right vertebral artery and dissected aneurysm in an antegrade fashion. A skull X-ray image was useful for detecting the change in appearance of the coils. The second embolization was successfully performed in the same manner. Based on this rare case, the authors emphasize that a careful angiographic analysis and complete internal trapping of the dissecting site are important in the treatment of the ruptured VADA.     

Effect of hypothermia on motor function of adult rats after neonatal hyperthermic hypoxic–ischemic brain insult

Regarding therapeutic hypothermia for human neonatal hyperthermic hypoxic–ischemic encephalopathy (HIE), we investigated the motor function of a neonatal hyperthermic HIE rat model, and also performed systemic hypothermia using the model. Forty-two neonatal Wistar rats at 7-days-old were used in this study. The left common carotid artery of 34 neonatal rats was ligated under isoflurane anesthesia. We also established a sham group (S group, n = 8). After 1-h recovery, all rats were exposed to 8% oxygen at an ambient temperature (T _a) of 40°C for 15 min. Following insult, 16 rats were placed in a chamber at a T _a of 30°C (H group) and the other 18 rats at a T _a of 37°C after arterial ligation (N group), and all rats in the S group were placed in a chamber at a T _a of 37°C for 12 h. A Rota-Rod test was performed involving all rats at 8 weeks old. The rod was rotated at 5, 5, and 7 rpm on three consecutive days, respectively. Rats in the N group stayed on the rotating rod for a significantly shorter period than those in S and H groups only on the second day of measurement. The width of the insulted hemisphere in N group rats was significantly smaller than those in S and H groups. There was no significant correlation between S and H groups regarding the motor function and anatomy. These results suggest that neonatal hyperthermic hypoxic–ischemic insult impairs the motor function, which may be rescued by systemic hypothermia after insult.     

Choice based on plausible reasons

This study tested the prediction that preferences induced by hidden factors would be justified and even accelerated by other factors that seem to be plausible determinants as causes but, in fact, do not have any influence on the preferences. Participants were repeatedly exposed to a variety of product logos of detergents and then asked to choose one from a pair of detergents with different logos. For half of the participants, information on product quality was available at choice; for the other half, only logos were available. The participants showed a tendency to prefer detergents with the logos that were more frequently exhibited, and this tendency was stronger when information was available about the product quality. The participants seemed to believe that they based their decisions on the relative superiority of quality between the pairs as well as their logos. Provided with convincing, but incorrect, reasons to make a choice, the participants were encouraged to select the detergents whose attractiveness had actually been manipulated by exposing the participants to their logos.