Pregnancy Associated Breast Cancer (PABC) manifests during pregnancy or within a year following delivery. We sought to investigate differences in management, outcome, clinical, histopathology and immunohistochemistry (IHC) characteristics of PABC and matched controls in a retrospective case control study. PABC and control patients were selected from breast cancer cases of women ≤45 years, diagnosed in the

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This paper reviews milestones in antidotal therapies for cyanide (CN) spanning early remedies, current antidotal systems and research towards next generation therapies. CN has been a part of plant defense mechanisms for millions of years. It became industrially important in the nineteenth century with the advent of CN assisted gold mining and the use of CN as a pest control agent. The biochemical basis of CN poisoning was actively studied and key mechanisms were understood as early as 1929. These fundamental studies led to a variety of antidotes, including indirect CN binders that generate methemoglobin, direct CN binders such as hydroxocobalamin, and sulfur donors that convert CN to the less toxic thiocyanate. Research on blood gases at the end of the twentieth century shed new light on the role of nitric oxide (NO) in the body. The discovery of NO's ability to compete with CN for enzymatic binding sites provided a previously missed explanation for the rapid efficacy of NO generating antidotes such as the nitrites. Presently used CN therapies include: methemoglobin/NO generators (e.g., sodium nitrite, amyl nitrite, and dimethyl aminophenol), sulfur donors (e.g., sodium thiosulfate and glutathione), and direct binding agents [(e.g., hydroxocobalamin and dicobalt salt of ethylenediaminetetraacetic acid (dicobalt edetate)]. A strong effort is being made to explore novel antidotal systems and to formulate them for rapid administration at the point of intoxication in mass casualty scenarios. New antidotes, formulations, and delivery systems are enhancing bioavailability and efficacy and hold promise for a new generation of improved CN countermeasures.

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Abstract. The objective of the present study was to investigate the effect of the pellet core materials isomalt, sugar, and microcrystalline cellulose on the in vitro drug release kinetics of coated sustainedrelease pellets as well as to evaluate the influence of different ratios of polymethacrylate copolymers exhibiting different permeability characteristics on the drug release rate. For characterization of the drug release process of pellets, the effect of osmolality was studied using glucose as an osmotically active agent in the dissolution medium. The pellet cores were layered with diclofenac sodium as model drug and coated with different ratios of Eudragit® RS30D and Eudragit® RL30D (ERS and ERL; 0:1 and 0.5:0.5 and 1:0 ratio) in a fluid bed apparatus. Physical characteristics such as mechanical strength, shape, and size proved that the inert cores were adequate for further processing. The in vitro dissolution tests were performed using a USP Apparatus I (basket method). The results demonstrated that, besides the ratio of the coating polymers (ERS/ERL), the release mechanism was also influenced by the type of starter core used. Sugar-and isomalt-type pellet cores demonstrated similar drug release profiles.

This study focused on the solubility enhancement and the in vivo antidotal efficacy testing of a new potential cyanide (CN) countermeasure, dimethyl trisulfide (DMTS). Various FDA approved cyclodextrins (HPβCD, RMβCD, HPγCD), cosolvents (ethanol, polyethylene glycols, propylene glycol), surfactants (cremophor EL, cremophor RH 40, sodium cholate, sodium deoxycholate, polysorbate 80) and their combinations were applied. Based on the solubility enhancing potential of the tested systems, polysorbate 80 was chosen for further in vivo efficacy studies. A composition comprising 15% polysorbate 80 and 50 mg/ml DMTS with the applied DMTS dose of 100 mg/kg provided a therapeutic antidotal protection of 3.4 × LD. For comparison, the present therapy of sodium thiosulfate (TS) with the dose of 100 mg/kg provided only 1.1 × LD protection, and at the dose of 200 mg/kg, the LD was enhanced by 1.3 times. No difference in the therapeutic protection by DMTS was detected when the concentration of polysorbate 80 was increased to 20% (3.2 × LD protection). These data demonstrate the potential importance of DMTS as a CN countermeasure, and the formulation comprising polysorbate 80 provides the base of an injectable intramuscular dosage form that can later serve as a CN antidotal kit suitable for mass scenario.

Skin metastatization of internal cancers are rare and a few studies are available analyzing its clinicopathological features. The reported incidence of skin metastasis is influenced by two factors: the relative proportion of cancers covered by skin in the various cohorts and the large differences in the prevalences of various cancer types. Futhermore, the anatomical distribution of skin metastases of various cancer types is aslo not well known. Therefore we have collected a skin metastasis cohort of biopsy and authopsy cases (n=80) from the archive of our department and analysed its clinicopathologic features. The adjusted skin metastasis prevalence data of various inner cancers indicated that kidney-, lung-and colorectal cancers have a strong positive preference for skin metastatisation while pancreatic cancer has a negative one. We have provided evidences that lower gastrointestinal-and genitourinary cancers preferred infradiaphragmatic skin regions unlike upper gastrointestinal cancers while lung-and kidney cancers preferred supradiaphragmatic regions. We have also detected that ventral skin regional metastasis is slightly more prevalent irrespective of the cancer type. Our study provide the first statistical data for the variations in skin preference of metastatisation among various cancer types as well as for the significant variations in their regional distributions.