GABAergic Interneuron Differentiation in the Basal Forebrain Is Mediated through Direct Regulation of Glutamic Acid Decarboxylase Isoforms by Dlx Homeobox Transcription Factors.

GABA is the key inhibitory neurotransmitter in the cortex but regulation of its synthesis during forebrain development is poorly understood. In the telencephalon, members of the distal-less (Dlx) homeobox gene family are expressed in, and regulate the development of, the basal ganglia primodia from which many GABAergic neurons originate and migrate to other forebrain regions. The Dlx1/Dlx2 double knock-out mice die at birth with abnormal cortical development, including loss of tangential migration of GABAergic inhibitory interneurons to the neocortex (Anderson et al., 1997a). We have discovered that specific promoter regulatory elements of glutamic acid decarboxylase isoforms (Gad1 and Gad2), which regulate GABA synthesis from the excitatory neurotransmitter glutamate, are direct transcriptional targets of both DLX1 and DLX2 homeoproteins in vivo Further gain- and loss-of-function studies in vitro and in vivo demonstrated that both DLX1 and DLX2 are necessary and sufficient for Gad gene expression. DLX1 and/or DLX2 activated the transcription of both Gad genes, and defects in Dlx function disrupted the differentiation of GABAergic interneurons with global reduction in GABA levels in the forebrains of the Dlx1/Dlx2 double knock-out mouse in vivo Identification of Gad genes as direct Dlx transcriptional targets is significant; it extends our understanding of Dlx gene function in the developing forebrain beyond the regulation of tangential interneuron migration to the differentiation of GABAergic interneurons arising from the basal telencephalon, and may help to unravel the pathogenesis of several developmental brain disorders.SIGNIFICANCE STATEMENT GABA is the major inhibitory neurotransmitter in the brain. We show that Dlx1/Dlx2 homeobox genes regulate GABA synthesis during forebrain development through direct activation of glutamic acid decarboxylase enzyme isoforms that convert glutamate to GABA. This discovery helps explain how Dlx mutations result in abnormal forebrain development, due to defective differentiation, in addition to the loss of tangential migration of GABAergic inhibitory interneurons to the neocortex. Reduced numbers or function of cortical GABAergic neurons may lead to hyperactivity states such as seizures (Cobos et al., 2005) or contribute to the pathogenesis of some autism spectrum disorders. GABAergic dysfunction in the basal ganglia could disrupt the learning and development of complex motor and cognitive behaviors (Rubenstein and Merzenich, 2003).

Seroprevalence of hepatitis B virus among hemodialysis patients in Bushehr province, southern Iran: HBV seroprevalence in hemodialysis patients.

BACKGROUND: Hepatitis B virus (HBV) infection is still reported from adult hemodialysis units. OBJECTIVES: To determine the prevalence of anti-HBs antibody in hemodialysis patients and the correlation between levels of anti-HBs antibody with other factors. PATIENTS AND METHODS: HBsAg, anti-HBs and anti-HBc antibodies level in 119 hemodialysis patients were evaluated by enzyme-linked immunosorbent assay. RESULTS: Seroconversion (anti-HBs antibody >10 IU/L) was found in 22 patients. Minimum protective antibody level was found in patients aged ≥60 years. Statistically significant correlation was not found between anti-HBs antibody and gender. Ten (8.4%) patients had abnormal ALT and/or AST. Prevalence of HBsAg, anti-HBc antibody, HBeAg and anti-HBe antibody were found in 8 (6.72%), 24 (25.16%), 2 (1.68%) and 3 (2.52%) patients, respectively. CONCLUSIONS: Periodic assessment of anti-HBs antibody level is strongly recommended in patients undergoing hemodialysis.

Antibacterial susceptibility patterns of Porphyromonas gingivalis isolated from chronic periodontitis patients

Objectives: To test the antimicrobial sensitivity of Porphyromonas gingivalis to a panel of eight orally administrable antibiotics in chronic periodontal diseases and to evaluate factors associated with periodontitis in adultpatients.Study Design: A total of fifty strains of P. gingivalis were isolated from one hundred and twenty adult patients with chronic perio-dontitis. Identification of bacteria was carried out by anaerobic culture and biochemical tests.Selected colonies of P. gingivalis were used to evaluate the antibacterial activities of penicillin, metronidazole,amoxicillin, amoxicillin/clavulanic acid, clindamycin, doxy-cycline, ciprofloxacin and azithromycin.Results: Most of the patients were female, age ranging between 40 to 50 years. Majority of the patients frequently had scaling and depths of periodontal pockets in infected teeth were 5-8 mm and most of them had hemorrhageduring sampling. Susceptibility testing revealed a sensitivity of 100% of P. gingivalis to azithromycin, doxycyclineand amoxicillin/clavulanic acid but lower susceptibilities were found for the rest of antibiotic agents evaluated.Conclusions: Frequent scaling in women aged between 40-50 years had positive correlation with chronic periodontitis.The application of antibiotics in conjuction with mechanical debridation, may reflect in the level of resistance of P. gingivalis in patients with chronic periodontal infections. This could suggest periodical antibiotic susceptibility testing is necessary to determine the efficacy of antimicrobial agents if the perfect curing of chronicperiodontal diseases after mechanical debridation is meant. Further clinical studies are required to confirm thein vitro results. The only limitation in this study was identification of bacteria to species rather than subspecies level (AU)

Association between existence of integrons and multi-drug resistance in Acinetobacter isolated from patients in southern Iran.

Nosocomial infections caused by multi-drug resistant Acinetobacter pose a serious problem in many countries. This study aimed at determining the antibiotic susceptibility patterns and prevalence of different classes of integrons in isolated Acinetobacter. In addition, the association between production of specific bands in PCR assay and magnitude of multi-drug resistance was investigated. In total, 88 Acinetobacter strains were isolated from patients from October 2008 through September 2009. The Minimal inhibitory concentration (MIC) of 12 antibiotics conventionally used in clinics against the isolates, was determined by E-test method. The existence of integron classes was investigated by PCR assay through the amplification of integrase genes. The most effective antibiotic against Acinetobacter was colistin with 97.7% activity, followed by imipenem (77.3%) and meropenem (72.7%). The presence ofintegron classes 1 and 2 in 47 (53.4%) isolates was confirme, However, no class 3 was detected. The proportion of class 1, compared with class 2, was high (47.7% vs. 3.4%). The association between multi-drug resistance to norfloxacin, ceftazidime, gentamicin, ciprofloxacin, cefepime and amikacin and the presence of integrons was statistically significant. However, the association was not remarkable in many of the isolates which exhibited resistance to the rest of antibiotics. This may imply that in addition to integrons, other resistance determinants such as transposon and plasmid may also contribute to resistance. To reduce the pressure on sensitive isolates, comprehensive control measures should be implemented. Furthermore, wise application of effective antibiotics could help alleviate the situation. Colistin is the most effective antibiotic in vitro against Acinetobacter.

Antibacterial susceptibility patterns of Porphyromonas gingivalis isolated from chronic periodontitis patients.

OBJECTIVES: To test the antimicrobial sensitivity of Porphyromonas gingivalis to a panel of eight orally administrable antibiotics in chronic periodontal diseases and to evaluate factors associated with periodontitis in adult patients. STUDY DESIGN: A total of fifty strains of P. gingivalis were isolated from one hundred and twenty adult patients with chronic perio-dontitis. Identification of bacteria was carried out by anaerobic culture and biochemical tests. Selected colonies of P. gingivalis were used to evaluate the antibacterial activities of penicillin, metronidazole, amoxicillin, amoxicillin/clavulanic acid, clindamycin, doxy-cycline, ciprofloxacin and azithromycin. RESULTS: Most of the patients were female, age ranging between 40 to 50 years. Majority of the patients frequently had scaling and depths of periodontal pockets in infected teeth were 5-8 mm and most of them had hemorrhage during sampling. Susceptibility testing revealed a sensitivity of 100% of P. gingivalis to azithromycin, doxycycline and amoxicillin/clavulanic acid but lower susceptibilities were found for the rest of antibiotic agents evaluated. CONCLUSIONS: Frequent scaling in women aged between 40-50 years had positive correlation with chronic periodontitis. The application of antibiotics in conjuction with mechanical debridation, may reflect in the level of resistance of P. gingivalis in patients with chronic periodontal infections. This could suggest periodical antibiotic susceptibility testing is necessary to determine the efficacy of antimicrobial agents if the perfect curing of chronic periodontal diseases after mechanical debridation is meant. Further clinical studies are required to confirm the in vitro results. The only limitation in this study was identification of bacteria to species rather than subspecies level.

Ventilator-associated pneumonia in Iranian intensive care units.

INTRODUCTION: Nosocomial pneumonia (NP) and ventilator associated pneumonia (VAP) occur most frequently in intensive care units (ICU). This study seeks to determine the etiological agents of NP and VAP along with their antibacterial susceptibility patterns, and to evaluate the factors contributing to patient mortality. The impact of appropriate therapy in terms of three parameters (body temperature, PaO2/FiO2 ratio and leukocyte count) was also assessed. METHODOLOGY: This study involved 836 adult patients admitted to ICUs at the Nemazee Hospital, Shiraz, Iran, over nine months during 2008 and 2009. The inclusion criterion was the commencement of infection at least 48 hours following hospital admission. Clinical parameters including core temperature, leukocyte count. and PaO2/FiO2 ratio were evaluated. Antibiotic sensitivities of the isolated bacteria to a panel of antibiotics were determined using E-test. RESULTS: Of 836 cases, only 58 (6.9 %) cases of NP were diagnosed, of which 42 (72 %) were VAP. A. baumannii, MRSA, P. aeruginosa and MSSA were the most prevalent bacteria. Significant correlations between previous antibiotic therapy (p = 0.04), use of corticosteroids (p = 0.02) and attributable mortality were found. A strong correlation between fever abatement and the ratio of PaO2/FiO2 with responses to treatment and outcomes was also evident. CONCLUSIONS: Combined treatment with meropenem/imipenem, ciprofloxacin and vancomycin seems to be appropriate and could cover all possible infective agents. To reduce mortality rate, reasonable prescription of antibiotics and corticosteroids could be effective. Furthermore, adopting a strategy to reduce body temperature and PaO2/FiO2 ratio could be beneficial in patients' outcomes.

Characterization of SCCmec types and antibacterial susceptibility patterns of methicillin-resistant Staphylococcus aureus in Southern Iran.

A total of 156 methicillin-resistant Staphylococcus aureus (MRSA) isolates from patients hospitalized in southern Iran were tested for staphylococcal cassette chromosome mec (SCCmec) types and antibacterial susceptibility patterns between May 2008 and May 2009. Type III SCCmec was the most prevalent (116, 74.3%), followed by mec types A (147 bp only; 11, 7.1%), IVa (8, 5.1%), IVc (7, 4.5%), IVd and V (4, 2.6%), and II (1, 0.6%). Class A mec and type III ccr and mec complexes were also predominant. All isolates were found to be sensitive to vancomycin, teicoplanin, linezolid, quinupristin-dalfopristin, mupirocin, and fusidic acid. However, reduced sensitivity of these MRSA isolates to other antibiotics, including rifampin, co-trimoxazole, clindamycin, cephalexin, tetracycline, ciprofloxacin, erythromycin, and gentamicin, was also observed. The predomination of type III SCCmec could be due to the antibiotic pressure which facilitated its clonal selection and dissemination. The present findings are indicative of the existence of community-acquired types (IV, V) in the hospitals studied, therefore comprehensive and periodic control measures and rational prescription of appropriate antibiotics are highly recommended to reduce antibiotic resistance.