Beta-lactamase stability and antibacterial activity of cefpirome alone and in combination with other antibiotics

The antibacterial activity of cefpirome (HR810), a new cephalosporin, was compared with that of other "third-generation" cephalosporins, as well as cefuroxime, piperacillin and gentamicin. Cefpirome was the most active beta-lactam antibiotic against Gram-negative bacteria. The MIC90 for Enterobacteriaceae was always less than 0.5 ml/l except for Enterobacter species. The MIC90 against Pseudomonas species was 2 mg/l, which was equal to that of ceftazidime and gentamicin. Cefpirome was also more active than the other beta-lactam antibiotics against Staphylococcus aureus. A relatively high frequency of synergy was observed when cefpirome was combined with aminoglycosides against both Gram-positive and Gram-negative bacteria. No antagonism was detected. This antibiotic was very stable to both plasmid- and chromosomally-mediated beta-lactamases. It was more resistant to Enterobacter cloacae P99 enzyme than ceftazidime, cefotaxime and cefotetan. Its stability to the Klebsiella K1 beta-lactamase was more than that of cefotaxime and ceftriaxone but slightly less than that of ceftazidime and latamoxef. MBC90 values for cefpirome were generally less than twice the corresponding MIC values.     

The Burden of Stroke in Kurdistan Province,Iran From 2011 to 2017

ObjectivesThe aim of this study was to calculate the burden of stroke in Kurdistan Province, Iran between 2011 and 2017.MethodsIncidence data extracted from the hospital information system of Kurdistan Province and death data extracted from the system of registration and classification of causes of death were used in a cross-sectional study. The World Health Organization method was used to calculate disability-adjusted life years (DALYs).ResultsThe burden of stroke increased from 2453.44 DALYs in 2011 to 5269.68 in 2017, the years of life lost increased from 2381.57 in 2011 to 5109.68 in 2017, and the years of healthy life lost due to disability increased from 71.87 in 2011 to 159.99 in 2017. The DALYs of ischaemic stroke exceeded those of haemorrhagic stroke. The burden of disease, new cases, and deaths doubled during the study period. The age-standardised incidence rate of ischaemic stroke and haemorrhagic stroke in 2017 was 21.72 and 20.72 per 100 000 population, respectively.ConclusionsThe burden of stroke is increasing in Kurdistan Province. Since health services in Iran are based on treatment, steps are needed to revise the current treatment services for stroke and to improve the quality of services. Policy-makers and managers of the health system need to plan to reduce the known risk factors for stroke in the community. In addition to preventive interventions, efficient and up-to-date interventions are recommended for the rapid diagnosis and treatment of stroke patients in hospitals. Along with therapeutic interventions, preventive interventions can help reduce the stroke burden.     

Relationship between stuttering severity in children and their mothers speaking rate.

CONTEXT AND OBJECTIVE: Stuttering is a complex disease that influences occupational, social, academic and emotional achievements. The aim of this study was to correlate the stuttering severity index with speaking rates of mothers and children. DESIGN AND SETTING: Cross-sectional study, at the child rehabilitation clinics of Tehran city. METHODS: 35 pairs of mothers and their children who stuttered were studied. There were 29 boys and six girls, of mean age 8.5 years (range: 5.1-12.0). Speech samples from the mother-child pairs were audiotaped for approximately 15 minutes, until a reciprocal verbal interaction had been obtained. This sample was then analyzed in accordance with a stuttering severity index test and speaking rate parameters. RESULTS: The research results outlined a significant relationship between the mothers speaking rate and their childrens stuttering severity. CONCLUSION: The results suggest that the mothers speaking rate should be incorporated in the assessment and treatment of stuttering.     

Endoscopic cyst fenestration outcomes in children one year of age or less

The use of endoscopic fenestration (EF) is becoming an increasingly common treatment for symptomatic intracranial cysts. Very little data exist regarding outcomes for this procedure in children 1 year of age or younger. We retrospectively reviewed the clinical outcomes of 8 children 1 year of age or less treated at our institution with endoscopic cyst fenestration. The mean follow-up was roughly 2.5 years. These data were combined with 17 other cases obtained from the published literature. EF was successful in rendering patients shunt-free or minimizing the number of ventricular catheters in 18 of 26 operations. There were 8 outright failures -- two in 1 patient. Given the risks and complications of cerebrospinal fluid shunting in children less than 1 year of age, we advocate the consideration of EF as initial treatment of symptomatic intracranial cysts.     

Identification of novel metabolites of pioglitazone in rat and dog

1. Four new metabolites of pioglitazone were identified by liquid chromatography-mass spectrometry (LC-MS/MS) as being formed by hydroxylation (M-VII and M-VIII), opening of the thiazolidinedione ring (M-X) and by desaturation of the terminal ethyl side chain or tether ethoxy moiety (M-IX), respectively. The structure of one of the hydroxylated metabolites (M-VII) was confirmed by chemical modification using the Jones reaction. 2. Oxidative cleavage of the thiazolidinedione ring is a novel pathway not previously reported for pioglitazone. 3. The hydroxylated M-VII was detected in incubations with rat, dog and human liver and kidney microsomes, and in plasma from rats and dogs dosed orally with [(3)H]pioglitazone. 4. The carboxylic acid derivative of M-VII (M-V) and its taurine conjugate were the major radioactive components in dog bile.     

Structure-activity studies of ground- and transition-state analogue inhibitors of cyclophilin

Peptidyl-prolyl isomerases (PPIases) are ubiquitous cellular enzymes that play roles in cellular signaling and protein folding. In addition, these proteins are the receptors for the widely used immunosuppressants cyclosporin A and FK506. We report the first structure-activity studies of de novo designed inhibitors of cyclophilin, the cellular target of cyclosporin A. Our mechanism-based inhibitors were modeled on the ground- and transition-state structures of proline-containing peptides, the natural substrates of the enzyme. Both ground-state analogues 1 and transition-state analogues 2 were prepared as single enantiomers from L-proline following a "self-reproduction of chirality" procedure. The binding affinities of the analogues for the active site of cyclophilin were measured by a fluorescence perturbation assay. While the transition-state analogues 2 did not display significant avidity for the active site (K(d) = 77 microM for 2b), several ground-state analogues bound to the enzyme with low micromolar affinity (K(d) = 1.5 microM for 1e). These results proclaim that properly designed small molecular weight molecules can form strong complexes with cyclophilin and may find use as probes in cell biology and as therapeutic agents.     

The nociceptive and anti-nociceptive effects of white mineral trioxide aggregate

Aim  To assess the nociceptive and antinociceptive effects of white mineral trioxide aggregate (WMTA) using the orofacial formalin test in rats.
Methodology  Rats ( n  = 10 in each group) were separately injected into the ipsilateral upper lip with either 40 μL of a 2.5% formalin solution and eugenol (50 mg kg⁻¹) or WMTA (5, 10 and 20 mg dissolved in 0.2 mL saline) alone. In a second experiment to evaluate antinociception effects, 15 min prior to formalin injection, rats were pre-treated with either white ProRoot MTA (20 mg dissolved in 0.2 mL saline) or eugenol. The time each rat spent rubbing the injected site with its paw, as an index of nociception, was recorded for a period of 45 min.
Results  Administration of 40 μL white ProRoot MTA (5, 10 and 20 mg per 0.2 mL) alone did not produce any significant nociceptive response. Moreover, prior treatment with WMTA caused significant ( P  < 0.001) inhibition of formalin-induced nociception. Injection of eugenol (50 mg kg⁻¹) provoked the first phase of a nociceptive response, although its intensity was reduced compared with that produced by formalin. Pre-treatment with eugenol significantly ( P  < 0.0001) inhibited the induction of nociception by formalin. Comparison of the behavioural responses observed in WMTA and eugenol-treated rats alone or in combination with formalin revealed that WMTA did not only induce pain behaviour but also prevented formalin-induced nociception.
Conclusion  White mineral trioxide aggregate, when compared with eugenol, was more effective in treating nociceptive pain in the orofacial formalin test.