Piperazine designer drugs elicit toxicity in the alternative in vivo model Caenorhabditis elegans

Piperazine designer drugs are a group of synthetic drugs of abuse that have appeared on the illicit market since the second half of the 1990s. The most common derivatives are 1-benzylpiperazine (BZP), 1-(4-methoxyphenyl)piperazine (MeOPP) and 1-(3,4-methylenedioxybenzyl)piperazine (MDBP). They can be consumed as capsules, tablets, but also in powder or liquid forms. Generally, although less potent than amphetamines, piperazines have dopaminergic and serotonergic activities. The aim of this work was to evaluate the toxic effects of BZP, MeOPP and MDBP using Caenorhabditis elegans as in vivo model for acute toxicity, development, reproduction and behavior testing. The LC₅₀ for BZP, MeOPP and MDBP were 52.21, 5.72 and 1.22 mm , respectively. All concentrations induced a significant decrease in the body surface of the worms, indicating developmental alterations, and decrease in the brood size. Worms exposed to piperazine designer drugs also presented a decrease in locomotor activity and mechanical sensitivity, suggesting the possible dysfunction of the nervous system. Neuronal damage was confirmed through the decrease in fluorescence of BY200 strains, indicating loss of dopaminergic transporters. In conclusion, we suggest that piperazine designer drugs lead to neuronal damage, which might be the underlying cause of the altered behavior observed in humans.     

Computational simulation of projectile injuries to human parietal bone using finite element analysis

The aim of this study was to evaluate the morphological and biomechanical characteristics of a wound entrance on the parietal bone from the impact of projectiles presenting three different calibres. Three-dimensional finite element models of dry human skull and of three projectiles with calibres .380 Auto, .40 S&W and 9 × 19 mm Luger were obtained. These geometries were used to perform a simulation of projectile impact on the parietal bone by the finite element method. We calculated the morphological aspect of the wounds on the external bone surface, the equivalent von Mises stress and the kinetic energy loss. The wounds from the 9 × 19 mm and .380 calibres presented a circular aspect, while the wound from the .40 calibre presented an oval aspect. The 9 × 19 mm caused a major wound area compared with the other calibres. The maximum von Mises stress in the bone was higher from the .40 calibre penetration, and the .380 had the major kinetic energy loss. In conclusion, the 9 × 19 mm and .380 presented similarity in the shape of the entrance hole. The projectile with 9 × 19 mm calibre seems to have greater penetration power and the .40 S&W projectile greater power of destruction and dissipation of energy.     

Factors associated with pregnancy intention among women who have experienced a short birth interval: findings from the 2009 to 2011 Mississippi and 2009 Tennessee Pregnancy Risk Assessment Monitoring System

Purpose

One-third of all pregnancies in the United States are conceived within 18 months of a prior live birth. Preventing unintended pregnancies may help to decrease the prevalence of pregnancies with these short interpregnancy intervals. However, data on factors associated with pregnancy intention among women who have had short birth intervals are sparse. Pregnancy Risk Assessment Monitoring System data were used to further evaluate these associations.

Antioxidant treatment prevented late memory impairment in an animal model of sepsis

OBJECTIVE: Assess the effect of antioxidant treatment on late memory impairment and early hippocampus oxidative stress after cecal ligation and perforation. SUBJECTS: Male Wistar rats. INTERVENTIONS: Rats underwent sham operation or cecal ligation and perforation. Animals that underwent cecal ligation and perforation were divided into groups: 1) treated with basic support (50 mL/kg saline, 30 mg/kg ceftriaxone, and 25 mg/kg clindamycin every 6 hrs), 2) treated with basic support plus N-acetylcysteine (20 mg/kg N-acetylcysteine at 3, 6, 12, 18, and 24 hrs after cecal ligation and perforation), 3) treated with basic support plus deferoxamine (20 mg/kg deferoxamine at 3 and 24 hrs after cecal ligation and perforation), 4) treated with basic support plus N-acetylcysteine and deferoxamine, or 5) treated with N-acetylcysteine plus deferoxamine. MEASUREMENTS AND MAIN RESULTS: On days 10 and 30 after surgery, the animals underwent behavioral tasks: inhibitory avoidance task, habituation to an open field, and continuous multiple-trials step-down inhibitory avoidance task. The sepsis group showed significantly decreased performance in latency retention compared with the sham group in the inhibitory avoidance task. In the open-field task, the sepsis group presented memory impairment after sepsis. In the continuous multiple-trials step-down inhibitory avoidance task, the sepsis group showed a significant increase in the number of training trials required to reach the acquisition criterion. All these memory impairments were prevented by N-acetylcysteine plus deferoxamine treatment, but not its isolate use. In addition, the combined use of antioxidants attenuated oxidative damage in hippocampus 6 hrs after sepsis induction. CONCLUSIONS: Antioxidant treatment prevented the development of late cognitive deficits in an animal model of sepsis.     

Opioid-sparing anesthesia and patient-reported outcomes after open gynecologic surgery: a historical cohort study

Canadian Journal of Anesthesia/Journal canadien d'anesthésie - Dexmedetomidine and ketamine may be administered intraoperatively as continuous infusions to provide opioid-sparing...     

EXPERIMENTAL MODEL FOR TREATMENT OF EXTENDED SPECTRUM BETALACTAMASE PRODUCING-KLEBSIELLA PNEUMONIAE

Background

Animal models are useful to evaluate the efficacy of antimicrobials in experimental sepsis.

Aim

To elucidate the steps of producing an experimental model for the treatment of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae sepsis

Methods

Several ESBL inoculums ranging from 1.5x10⁹ colony-forming units per milliliter (CFU/mL) to 2.0x10¹⁰CFU/mL were administered by peritoneal injection in adults Wistar rats. Outcomes and microbiological data of quantitative peritoneal and blood cultures were observed in untreated animals. Animals which received 2.0x10¹⁰CFU/mL inoculums were treated with single meropenem dose (30mg/kg) after one hour and those which received 1.0x10¹⁰CFU/mL inoculums were treated immediately with three doses of meropenem 50 mg/kg. Outcomes were observed for 24 hours after inoculation.

Results

Solutions with 1.5 x10⁹ and 6.0x10⁹ CFU/mL were not lethal within 24 hours. Inoculums of 1.0x10¹⁰CFU/mL were lethal in 80% and solutions with 2.0x10¹⁰ CFU/mL were lethal in 100% of animals. ESBL lethal sepsis (1.0x10¹⁰CFU/mL) was treated immediately with 50 mg/kg of meropenem every eight hours for 24 hours and presented 40% mortality compared with 80% mortality of the control group (p=0.033). Quantitative cultures of peritoneal fluid presented 10⁴CFU/mL or less for treated animals compared to more than 10⁵ for untreated animals (p=0.001).

Conclusion

Inoculums of 1.0x10¹⁰CFU/mL achieved the best results to study a model of lethal sepsis and this model of treatment of carbapenem-susceptible Enterobacteriaceae can serve as control to further evaluation of treatment of carbapenemase-producing Enterobacteriaceae models.     

Characterization and Treatment of Local Recurrence Following Breast Conservation for Ductal Carcinoma In Situ

Purpose

The optimal treatment strategy for ductal carcinoma in situ (DCIS) continues to evolve and should consider the consequences of initial treatment on the likelihood, type, and treatment of recurrences.

Methods

We conducted a retrospective cohort study using two data sources of patients who experienced a recurrence (DCIS or invasive cancer) following breast-conserving surgery (BCS) for index DCIS: patients with an index DCIS diagnosed from 1997 to 2008 at the academic institutions of the National Comprehensive Cancer Network (NCCN; N = 88) and patients with an index DCIS diagnosed from 1990 to 2001 at community-based integrated healthcare delivery sites of the Health Maintenance Organization Cancer Research Network (CRN) (N = 182).

Results

Just under half of local recurrences in both cohorts were invasive cancer. While 40 % of patients in both cohorts underwent mastectomy alone at recurrence, treatment of the remaining patients varied. In the earlier CRN cohort, most other patients underwent repeat BCS (39 %) with only 18 % receiving mastectomy with reconstruction, whereas only 16 % had repeat BCS and 44 % had mastectomy with reconstruction in the NCCN cohort. Compared with patients not treated with radiation, those who received radiation for index DCIS were less likely to undergo repeat BCS (NCCN: 6.6 vs. 37 %, p = 0.001; CRN: 20 vs. 48 %, p = 0.0004) and more likely to experience surgical complications after treatment of recurrence (NCCN: 15 vs. 4 %, p = 0.17; CRN: 40 vs. 25 %, p = 0.09).

Conclusion

We found that treatment of recurrences after BCS and subsequent complications may be affected by the use of radiotherapy for the index DCIS. Initial treatment of DCIS may have long-term implications that should be considered.     

Reliability and longevity of implantable defibrillators

Journal of Interventional Cardiac Electrophysiology - We hypothesized that data in manufacturers’ product performance reports (PPRs) can provide clinically valuable ICD and cardiac...