Reappraisal of parenteral antimicrobial therapy for nontyphoidal Salmonella enteric infection in children.

Increasing antimicrobial resistance in nontyphoidal Salmonella (NTS) species complicates the use of antibiotics if indicated. We investigated the impact of antimicrobial resistance on clinical outcomes and discussed how to use antibiotics rationally. Hospitalized children in 2005-2006 with stool cultures positive for NTS were identified. The clinical and microbiological features were retrospectively reviewed. A total of 683 children were included [371 (54.3%) male; 89.5% <5 years of age]. Antibiotics were given to 56.5% of the patients; third-generation cephalosporin was the most commonly used drug class. Cases receiving antibiotics that were inactive in vitro did not have more complications than those receiving antibiotics active in vitro. Complications occurred in 7.9% of the patients, with bacteraemia being the most common (57.4%). Compared to the others, patients with longer febrile duration and higher C-reactive protein (CRP) levels (CRP ≥100 mg/L) were more frequently put on empirical antimicrobial therapy and had more complications. These patients usually had shorter hospitalization and duration of fever if antimicrobial agents that can reach high tissue concentrations in the intestinal mucosa were administered, such as fluoroquinolone or ceftriaxone. It is concluded that adequate antibiotics may be clinically beneficial to a subset of patients with high CRP and longer duration of fever among children with NTS enteritis. To prevent the induction of antibiotic resistance from this therapy, we suggested a short course (3-5 days) of intravenous ceftriaxone for such patients, which would lead to a faster clinical recovery.

Two novel mutations of the glycine receptor gene in a Taiwanese hyperekplexia family.

The authors report a Taiwanese family with autosomal recessive hyperekplexia. Two novel mutations, W96C (from the paternal allele) and R344X (from the maternal allele), which are located in exon 4 and exon 7 of the GLRA1 gene, were identified in this family. A series of electrophysiologic investigations were conducted in one of the probands, and the results suggest that the "startle center" is located subcortically.

Antagonism of free-radical-induced damage of adlay seed and its antiproliferative effect in human histolytic lymphoma U937 monocytic cells.

The goal of our current research was to investigate the antioxidative effects of methanolic extracts from different parts of adlay seed and their antiproliferative activity in malignant human cells. The methanolic extracts from different parts of adlay seeds were from the hull (AHM), testa (ATM), bran (ABM), and polished adlay (PAM). AHM exhibited greater capacity to scavenge superoxide anion radicals in the PMS-NADH system than ATM, ABM, or PAM. The scavenging capacities of AHM and ATM on hydrogen peroxides were about 20% at a dose of 250 microg/mL. Using the method of deoxyribose degradation to assess damage caused by hydroxyl radicals, AHM was found to inhibit damage in deoxyribose at a higher concentration. However, ATM, ABM, and PAM exhibited prooxidative activity at the same concentration. The inhibitory effect on enzymatic oxidation of xanthine to uric acid was found to follow the order AHM > ATM =. ABM. However, PAM was inactive. All test samples were positive for inhibition of TPA-induced free radical formation on neutrophil-like leukocytes and were found to follow the order AHM > ATM > ABM > PAM. When human histolytic lymphoma U937 monocytic cells were exposed to tert-butyl hydroperoxide, AHM protected the cells against the cytotoxicity caused by tert-butyl hydroperoxide. In addition, AHM exhibited antiproliferative activity against human histolytic lymphoma U937 monocytic cells in a dose-dependent manner. The antiproliferative properties of AHM appear to be attributable to its induction of apoptotic cell death as determined by flow cytometry. These results show that AHM displays multiple antioxidant effects and induces apoptosis of malignant human cells.

Recovery from inactivation of t-type ca2+ channels in rat thalamic neurons.

We studied the gating kinetics, especially the kinetics of recovery from inactivation, of T-type Ca(2+) channels (T-channels) in thalamic neurons. The recovery course is associated with no discernible Ca(2+) current and is characterized by an initial delay, as well as a subsequent exponential phase. These findings are qualitatively similar to previous observations on neuronal Na(+) channels and suggest that T-channels also must deactivate to recover from inactivation. In contrast to Na(+) channels in which both the delay and the time constant of the exponential phase are shortened with increasing hyperpolarization, in T-channels the time constant of the exponential recovery phase remains unchanged between -100 and -200 mV, although the initial delay is still shortened e-fold per 43 mV hyperpolarization over the same voltage range. The deactivating kinetics of tail T-currents also show a similar voltage dependence between -90 and -170 mV. According to the hinged-lid model of fast inactivation, these findings suggest that the affinity difference between inactivating peptide binding to the activated channel and binding to the fully deactivated channel is much smaller in T-channels than in Na(+) channels. Moreover, the inactivating peptide in T-channels seems to have much slower binding and unbinding kinetics, and the unbinding rates probably remain unchanged once the inactivated T-channel has gone through the initial steps of deactivation and "closes" the pore (with the activation gate). T-channels thus might have a more rigid hinge and a more abrupt conformational change in the inactivation machinery associated with opening and closing of the pore.

Analgesic effect of electric stimulation of peripheral nerves with different electric frequencies using the formalin test.

Although electroacupuncture (EA) has been widely used to treat pain, the optimal frequency of EA therapy remains unclear. The study sought to determine the effect of different EA frequencies in a Sprague-Dawley (SD) rat model of pain. Electric stimulation (ES) at frequencies of 2 Hz, 15 Hz or 100 Hz was applied to the ipsilateral or contralateral sciatic nerve of the injected hindpaw of SD rats. Formalin (50 microl, 5%) was subcutaneously injected into the plantar surface of the left hindpaw to induce a nociceptive response. Behavior, including licking and biting, was observed to have two distinct periods, an early phase during the first 5 mins and a late phase from 21-35 mins after injection. The total biting or licking count served as an Indicator of nociceptive response. Our results indicate that ES of the ipsilateral sciatic nerve at a frequency of 2 Hz or 15 Hz reduced the nociceptive responses in both the early and the late phases of the formalin test, whereas ES at 2 Hz had greater antinociceptive effect than ES at 15 Hz in the early phase. No similar analgesic effect in the early phase was observed for ES at 100 Hz. Both pretreatment with ES at 2 Hz and naloxone (3 mg/kg, s.c.) produced a greater antinociceptive response in the late phase than when ES at 2 Hz was delivered immediately after formalin administration. In addition, ES of the neck muscle or contralateral sciatic nerve at a frequency of 2 Hz also decreased licking and biting activity in both phases. The results of this study indicate that different analgesic mechanisms are involved in the response to ES at frequencies of 2 Hz, 15 Hz and 100 Hz, and that ES at 2 Hz has a greater analgesic effect on formalin-induced nociceptive response, especially when it is delivered prior to the onset of pain. The analgesic effect of ES may be mediated via a central origin in the supraspinal level. These findings suggest that 2 Hz may be a good frequency selection for clinical EA applications in analgesia, and that pretreatment with EA at 2 Hz may be an effective method to treat post-operative pain.

Molecular cloning, characterization and tissue expression of prophenoloxidase cDNA from the mosquito Armigeres subalbatus inoculated with Dirofilaria immitis microfilariae.

A cDNA encoding mosquito Armigeres subalbatus prophenol oxidase (As-pro-PO) was obtained by rapid amplification of cDNA ends-polymerase chain reaction (RACE-PCR) after Dirofilaria immitis inoculation. The 2205 bp As-pro-PO cDNA contains a 32 bp 5'-noncoding region, a 2055 bp open reading frame (685 amino acids), and a 118 bp 3'-noncoding region. Hydrophobic signal peptide for the endoplasmic reticulum targeting is not found in the NH2-terminal region. Two potential copper-binding domains, amino acids 197-245 and 345-412, are highly homologous to those of the other insect pro-POs. A 2.2 kb As-pro-PO transcript was identified by Northern blot analysis using D. immitis microfilariae-inoculated A. subalbatus. Both in situ hybridization and Northern blot analysis demonstrated that As-pro-PO mRNA was synthesized in mosquito haemocytes but not in other tissues, i.e. fat bodies, midguts and ovaries, etc.

In vitro activities of azithromycin, clarithromycin, and other antibiotics against Chlamydia pneumoniae.

The in vitro susceptibilities of Chlamydia pneumoniae isolates to macrolide, tetracycline, and quinolone antibiotics were determined. Tetracycline, clarithromycin, and erythromycin had the lowest MICs in the first cell culture passage. Azithromycin required the lowest concentration for complete inhibition of inclusion formation on the second pass into antibiotic-free medium, likely reflecting its high intracellular concentrations.

Postnatal development of cortical acetylcholinesterase-rich neurons in the rat brain: permanent and transient patterns.

The development of acetylcholinesterase (AChE) activity within cortical neurons of the rat brain was investigated using a histochemical method. The fate of these neurons in later stages of development was studied in animals in which AChE within cortical axons (mostly cholinergic) had been depleted by lesions of the cholinergic neurons of the basal forebrain or by injections of diisopropyl fluorophosphate. We designated neurons with medium to high intensity of reaction product as AChEH and neurons with a low intensity of reaction product as AChEL. Four groups of AChEH cortical neurons were detected: (1) AChEH Cajal-Retzius cells were present in layer I at birth (P0) and decreased steadily in number until none could be detected at P17 or thereafter. (2) AChEH neurons within layer VI and underlying white matter were present at P0, peaked in number and staining intensity at P8-P9, showed a moderate decrease in number at P11-P13 and a further decrease into adulthood. (3) AChEH polymorphic intracortical neurons appeared at P3-P4 in deep cortical layers and by P9 were present in layers II-VI. They continued to increase in number through P11-P14 at which time they displayed the adult pattern and were found in all cortical areas. (4) A large population of AChEH pyramidal neurons appeared at P1-P4, peaked at P8-P10 and was no longer visible at P21. In the adult cerebral cortex, few pyramidal neurons displayed AChE activity and these were almost always of the AChEL type. These results indicate that the AChE within cortical neurons is developmentally regulated and that the content of this enzyme helps to differentiate cortical neurons into distinct populations. The transient expression of AChE activity within cortical neurons suggests a role for this enzyme in the development of the cerebral cortex.

Effects of two antibiotic regimens on course and persistence of experimental Chlamydia pneumoniae TWAR pneumonitis.

We studied the effects of two antibiotic regimens on the course of Chlamydia pneumoniae infection in the lungs of Swiss Webster mice. After intranasal challenge with isolates AR-388 (1.3 x 10(7) inclusion-forming units per mouse) and AR-39 (1.5 x 10(6) inclusion-forming units per mouse), groups of animals were treated with either doxycycline (10 mg/kg of body weight once a day for 3 days), azithromycin (10 mg/kg [single dose]), or saline. Responses were assessed by the isolation of organisms in cell culture, detection of TWAR DNA in lung tissues by PCR, and lung histology. Both regimens were effective in clearing infections induced by AR-388 (P = 0.02 and 0.007 for doxycycline and azithromycin, respectively) compared with controls. TWAR DNA was detected in 77 and 25% of culture-negative lungs 2 weeks after treatment of AR-388 and AR-39 infections, respectively. Histological changes showed interstitial pneumonitis and were similar over time for all groups. Single-dose azithromycin produced drug levels in lung tissues above the MICs for the test strains for a period three times longer than that of single-dose doxycycline. We concluded that short-term antibiotic regimens were successful for the treatment of experimental TWAR pneumonitis in mice. TWAR DNA was frequently recovered from lung tissues after apparently successful treatment.

Oral contraceptives do not alter the course of experimentally induced chlamydial salpingitis in monkeys.

BACKGROUND AND OBJECTIVES: The effects of oral contraceptive use on chlamydial infections and ensuing PID are not well understood. In this study, the effects of oral contraceptives on the clinical course of acute chlamydial salpingitis were investigated. STUDY DESIGN: Monkeys (n = 4) in which salpingeal auto-transplants had been established were given oral contraceptive pills consisting of a combination of estrogen and progesterone (Norlestrin 1/50, Parke-Davis, Ann Arbor, MI). After one complete cycle of hormone treatment, monkeys were inoculated with C. trachomatis serovar E in the subcutaneous salpingeal pockets while under continuous hormone treatment. Inoculated pockets were biopsied serially for isolation of organisms and histopathological evaluation. Two monkeys not given oral contraceptives were studied in parallel. RESULTS: The duration of infection as evidenced by recovery of organisms was not appreciably different between the treated and untreated monkeys. Chlamydia could be recovered from pocket tissues through day 10 post-infection in control and treated animals, and on day 14 post-infection in one of two control animals. Thereafter all isolation became negative. The inflammatory infiltrate consisted primarily of mononuclear cells (50-100 cells per 40 x field). CONCLUSIONS: Our results indicate that administration of oral contraceptives did not affect the duration of shedding of organisms nor the histopathology of acute chlamydial infection of the reproductive tract.

Comparison of ophthalmic silver nitrate solution and erythromycin ointment for prevention of natally acquired Chlamydia trachomatis.

During prospective studies of infants born vaginally to women with cervical Chlamydia trachomatis infection, we evaluated 27 infants given 0.5% erythromycin ointment and 93 given 1% silver nitrate solution as eye prophylaxis, according to the preference of the parents or delivery room personnel. The cumulative proportion of infants developing chlamydial conjunctivitis was 25% for both groups (P = 0.37, Mantel-Cox test). The cumulative proportion of infants developing chlamydial infection at any anatomic site was 74% for those given erythromycin and 70% for those given silver nitrate (P = 0.93). The two groups did not differ significantly in cumulative proportions developing nonchlamydial conjunctivitis. These results indicate that, as it is routinely used in our hospital, erythromycin ointment was not more effective than silver nitrate as prophylaxis against chlamydial conjunctivitis. The influence of delayed administration on efficacy of prophylaxis requires further evaluation.