Growth inhibition of MXT mammary carcinoma by enhancing programmed cell death (apoptosis) with analogs of LH-RH and somatostatin

BDF female mice inoculated with MXT mammary adenocarcinoma were treated for 30 days with microcapsules of the luteinizing hormone-releasing hormone (LH-RH) agonist D-Trp-6-LH-RH (releasing 25µg/day for 30 days), microcapsules of the somatostatin agonist RC-160 (liberating 25µg/day for one month), or the combination of these peptides. Bilateral surgical ovariectomy was performed in one group which served as an additional control. Tumor volume was measured weekly during the treatment period of 30 days. When tumor volume changes in the treated groups were compared to the corresponding changes in controls, the combination of D-Trp-6-LH-RH and RC-160 was the most effective in inhibiting tumor growth and approached the effect of surgical ovariectomy. At the conclusion of the experiment, tumor weights were also measured. All peptide analogs inhibited tumor weight by 42 to 63%. In the D-Trp-6-LH-RH treated group, ovarian weights and uterine weights decreased by 48% and 52%, respectively, as compared to controls. Histologically, the regressive changes in tumors caused by the treatment with RC-160, D-Trp-6-LH-RH and their combination were characterized by the coexistence of apoptosis (programmed cell death) and coagulation necrosis. The transition of apoptosis into coagulation necrosis was a common finding. The term apoptotic index is proposed for the ratio of tumorous glands containing apoptotic cells. The apoptotic index was higher in the treated groups than in the control.     

Non-synaptic receptors and transporters involved in brain functions and targets of drug treatment

Beyond direct synaptic communication, neurons are able to talk to each other without making synapses. They are able to send chemical messages by means of diffusion to target cells via the extracellular space, provided that the target neurons are equipped with high-affinity receptors. While synaptic transmission is responsible for the ‘what’ of brain function, the ‘how’ of brain function (mood, attention, level of arousal, general excitability, etc.) is mainly controlled non-synaptically using the extracellular space as communication channel. It is principally the ‘how’ that can be modulated by medicine. In this paper, we discuss different forms of non-synaptic transmission, localized spillover of synaptic transmitters, local presynaptic modulation and tonic influence of ambient transmitter levels on the activity of vast neuronal populations. We consider different aspects of non-synaptic transmission, such as synaptic–extrasynaptic receptor trafficking, neuron–glia communication and retrograde signalling. We review structural and functional aspects of non-synaptic transmission, including (i) anatomical arrangement of non-synaptic release sites, receptors and transporters, (ii) intravesicular, intra- and extracellular concentrations of neurotransmitters, as well as the spatiotemporal pattern of transmitter diffusion. We propose that an effective general strategy for efficient pharmacological intervention could include the identification of specific non-synaptic targets and the subsequent development of selective pharmacological tools to influence them.     

Standards of Evidence for Conducting and Reporting Economic Evaluations in Prevention Science

Over a decade ago, the Society for Prevention Research endorsed the first standards of evidence for research in preventive interventions. The growing recognition of the need to use limited resources to make sound investments in prevention led the Board of Directors to charge a new task force to set standards for research in analysis of the economic impact of preventive interventions. This article reports the findings of this group’s deliberations, proposes standards for economic analyses, and identifies opportunities for future prevention science. Through examples, policymakers’ need and use of economic analysis are described. Standards are proposed for framing economic analysis, estimating costs of prevention programs, estimating benefits of prevention programs, implementing summary metrics, handling uncertainty in estimates, and reporting findings. Topics for research in economic analysis are identified. The SPR Board of Directors endorses the “Standards of Evidence for Conducting and Reporting Economic Evaluations in Prevention Science.”     

Giant extradural sacral meningioma

We present the first case of primary benign fibrous meningioma restricted to the sacrum with no sign of recurrence after a long follow-up duration. This occurred in a 36-year-old man who initially presented with a 3-month history of right-sided sciatica. The tumour was successfully resected after three surgical procedures due to its high vascularity and technical difficulties. Sacroiliac joint stability was not disrupted, and he is still doing well clinically at 8 years follow-up.     

Airborne methylene diphenyl diisocyanate (MDI) concentrations associated with the application of polyurethane spray foam in residential construction

The primary objectives of this study were (a) to measure potential exposures of applicators and assistants to airborne methylene diphenyl diisocyanate (MDI), (b) to measure airborne concentrations of MDI at various distances from the spray foam application, and (c) to measure airborne MDI concentrations as a function of time elapsed since application. Other study objectives were, (a) to compare the results from filter and impinger samples; (b) to determine the particle size distribution in the spray foam aerosol; (c) to determine potential exposures to dichlorofluoroethane; and (d) to measure any off-gassing of MDI after the foam had fully cured. This study was conducted during application of spray polyurethane foam inside five single-family homes under construction in the United States and Canada.Spray foam applicators and assistants may be exposed to airborne MDI concentrations above the OSHA permissible exposure limit. At these concentrations, OSHA recommends appropriate respiratory protection during spray foam application to prevent airborne MDI exposures above established limits and to protect against exposure to dichlorofluoroethane (HCFC-141b). Airborne MDI concentrations decrease rapidly after foam application ceases. The highest airborne concentrations measured after 15 min and 45 min were 0.019 mg/m3 and 0.003 mg/m3, respectively. After 45 min, airborne concentrations were below the limit of quantitation (LOQ) of 0.036-microg per sample. For samples taken 24 hours after completion of foaming, results were also below the LOQ. Approximately two-thirds of the total mass of the airborne particles in the spray foam aerosol was greater than 3.5 microns in diameter. Airborne MDI concentrations determined by filter sampling methods were 6% to 40% lower than those determined by impinger methods.     

Endodontic and microsurgical treatments of maxillary lateral incisor dens invaginatus in combination with cone-beam-computed tomography fusion imaging

In this case report, we present the endodontic treatment and microsurgical intervention of dens invaginatus affecting a lateral incisor using cone-beam-computed tomography (CBCT). A 26-year-old woman visited us with a diagnosis of acute apical periodontitis in the upper right lateral incisor (tooth 12). Endodontic treatment of the tooth was carried out. Intraoral radiography provided limited information on the unusual anatomy of the pulp chamber and root canal system; therefore, preoperative CBCT was performed. At the 3-month recall, a radiograph revealed a 5-mm-diameter lateral transparency, and CBCT was, therefore, repeated to facilitate microsurgery treatment planning. A medical image-processing program was used to demonstrate the changes between the CBCT images obtained before and after root canal preparation. In conclusion, endodontic treatment of dens invaginatus is challenging even for endodontic specialists, because the therapy sometimes requires surgical intervention. The currently available novel three-dimensional imaging modalities may have importance in planning and following up the root canal treatment in such cases, especially when unforeseen complications arise.