On minimal non- MSP -groups

A finite group G is called an MSP-group if all maximal subgroups of the Sylow subgroups of G are Squasinormal in G. In this paper, wc give a complete classification of those groups which are not MSP-groups but whose proper subgroups are all MSP-groups.Скiнченну групу G називають MSP-групою, якщо всi максимальнi пiдгрупи силовських пiдгруп G є S-квазiнормальними в G. Наведено повну класифiкацiю груп, якi не є MSP-групами, але всi їх власнi пiдгрупи є MSP-групами

Blocking Drug Activation as a Therapeutic Strategy to Attenuate Acute Toxicity and Physiological Effects of Heroin

Heroin is a growing national crisis in America. There is an increasing frequency of heroin overdoses. All of the currently used therapeutic approaches to treatment of heroin abuse and other opioid drugs of abuse focus on antagonizing a brain receptor (particularly µ-opiate receptors). However, it has been known that the therapeutic use of certain µ-opiate receptor antagonist may actually increase heroin overdose. Once overdosed, heroin addicts may continue to get overdosed again and again until fatal. Here we report our design and validation of a novel therapeutic strategy targeting heroin activation based on our analysis of the chemical transformation and functional change of heroin in the body. An effective blocker of heroin activation, such as ethopropazine tested in this study, may be used as a standalone therapy or in combination with a currently available, traditional medications targeting µ-opiate receptors (e.g. naltrexone or its extended-release formulation Vivitrol). The combination therapy would be ideal for heroin abuse treatment as the effects of two therapeutic agents targeting two independent mechanisms are cooperative

A Quantitative LC-MS/MS Method for Simultaneous Determination of Cocaine and Its Metabolites in Whole Blood

As new metabolic pathways of cocaine were recently identified, a high performance liquid chromatography tandem mass spectrometry (LC–MS/MS) method was developed to simultaneously determine cocaine and nine cocaine-related metabolites in whole blood samples. One-step solid phase extraction was used to extract all of the ten compounds and corresponding internal standards from blood samples. All compounds and internal standards extracted were separated on an Atlantis T3 (100 Å, 3 μm, 2.1 mm × 150 mm I.D) column and detected in positive ion and high sensitivity mode with multiple reaction monitoring. This method was validated for its sensitivity, linearity, specificity, accuracy, precision, recovery, and stability. All of the ten compounds were quantifiable ranging from the lower limit of quantification (LLOQs) of ∼10 nM (1.9–3.2 ng/ml) to ∼1000 nM (190–320 ng/ml) without any interfering substance. Accuracy and precision were determined, and both of them were within the acceptance criteria of the United States (US) Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidelines. The recovery was above 66.7% for all compounds. Stability tests demonstrated the stability of compounds under different storage conditions in whole blood samples. The method was successfully applied to a pharmacokinetic study with co-administration of cocaine and alcohol in rats

Clinical Potential of an Enzyme-Based Novel Therapy for Cocaine Overdose

It is a grand challenge to develop a truly effective medication for treatment of cocaine overdose. The current available, practical emergence treatment for cocaine overdose includes administration of a benzodiazepine anticonvulsant agent (e.g. diazepam) and/or physical cooling with an aim to relieve the symptoms. The inherent difficulties of antagonizing physiological effects of drugs in the central nervous system have led to exploring protein-based pharmacokinetic approaches using biologics like vaccines, monoclonal antibodies, and enzymes. However, none of the pharmacokinetic agents has demonstrated convincing preclinical evidence of clinical potential for drug overdose treatment without a question mark on the timing used in the animal models. Here we report the use of animal models, including locomotor activity, protection, and rescue experiments in rats, of drug toxicity treatment with clinically relevant timing for the first time. It has been demonstrated that an efficient cocaine-metabolizing enzyme developed in our previous studies can rapidly reverse the cocaine toxicity whenever the enzyme is given to a living rat, demonstrating promising clinical potential of an enzyme-based novel therapy for cocaine overdose as a successful example in comparison with the commonly used diazepam

Residue Analysis and Exposure Assessment of Methylsiloxane Oligomers in Fried Chicken and French Fries

The fried food in fast food is deeply loved by consumers. However, with the increasing concern about the safety of volatile methylsiloxanes, the residue of oligomer monomer of methylsiloxanes from defoamer PDMS in fried food needs to be studied urgently. In this study, an efficient and sensitive method for the determination of methylsiloxane oligomers in fried chicken and French fries was established using QuEChERS-gas chromatography-tandem mass spectrometry (GC-MS/MS). A total of 33 fried chickens and 30 French fries purchased from fast food restaurants were analyzed and a preliminary exposure assessment using a point assessment method was carried out. The results showed that octamethyl cyclotetrasiloxane (D4)~hexamethyldisiloxane (D18) and decamethyl tetrasiloxane (L4)~triaconta methyltetradecasiloxane (L14) were detected, and the median total content of methylsiloxane oligomers in fried chicken (514.61 ng·g−1) was higher than that in French fries (83.4 ng·g−1). The estimated daily intake (EDI) of methylsiloxanes (molecular weight <1000) in fried chicken and French fries was 164.94 ng·kg−1·d−1 and 13.09 ng·kg−1·d−1, respectively, which was lower than the PDMS acceptable daily intake (ADI) (0.8 mg·kg−1·d−1). However, the potential hazards of some volatile methylsiloxanes such as D4~dodecamethyl cyclohexasiloxane (D6) need to be further investigated after long-term low dose intake and enrichment. This study provides a scientific basis for the safety evaluation and subsequent in-depth study of methylsiloxanes residues in fried food fast food

Structure-Based Discovery of mPGES-1 Inhibitors Suitable for Preclinical Testing in Wild-Type Mice as a New Generation of Anti-Inflammatory Drugs

Human mPGES-1 is recognized as a promising target for next generation of anti-inflammatory drugs without the side effects of currently available anti-inflammatory drugs, and various inhibitors have been reported in the literature. However, none of the reported potent inhibitors of human mPGES-1 has shown to be also a potent inhibitor of mouse or rat mPGES-1, which prevents using the well-established mouse/rat models of inflammation-related diseases for preclinical studies. Hence, despite of extensive efforts to design and discover various human mPGES-1 inhibitors, the promise of mPGES-1 as a target for the next generation of anti-inflammatory drugs has never been demonstrated in any wild-type mouse/rat model using an mPGES-1 inhibitor. Here we report discovery of a novel type of selective mPGES-1 inhibitors potent for both human and mouse mPGES-1 enzymes through structure-based rational design. Based on in vivo studies using wild-type mice, the lead compound is indeed non-toxic, orally bioavailable, and more potent in decreasing the PGE2 (an inflammatory marker) levels compared to the currently available drug celecoxib. This is the first demonstration in wild-type mice that mPGES-1 is truly a promising target for the next generation of anti-inflammatory drugs