Global Developments in Employee Benefits

The last 25 years have seen defined benefit plans increasingly been replaced by defined contribution (DC) arrangements. While the pace and shape of this change varies across countries, it is evident that we are living in a DC world. Yet the DC model is itself under challenge. The assumption of engaged consumers that accompanied the birth of DC has failed, and for both retirement and health benefits, there is a lingering question whether, in a world of low growth, stagnating incomes and increasingly diverse workforces, one-size-fits-all benefits plans can meet employees financial needs. Instead employers are increasingly expressing interest in moving to a next generation of benefits, one characterized by greater flexibility and choice, to encompass a broader range of employee needs. This paper discusses the emerging trends within occupational benefits, the forces that are driving these changes, and the challenges they pose

Components of the human-specific, p53-mediated “kill switch” tumor suppression mechanism are usurped by human tumors, creating the possibility of therapeutic exploitation

We recently reported our detection of an anthropoid primate-specific, adrenal androgen-dependent, “kill switch” tumor suppression mechanism that is triggered by the inactivation of the p53 tumor suppressor. This mechanism reached its highest expression only in humans as a result of the human-specific harnessing of fire, which resulted in an extraordinary increase in exposure to polycyclic aromatic hydrocarbons. This “kill switch” becomes inoperative in modern humans once they exceed the primitive human lifespan of 25-30 years, because lifespan has more than tripled in modern times, but the secretion curve for dehydroepiandrosterone sulfate remains fixed at the level required for the primitive human lifespan. Components of this “kill switch” are consequently usurped by human tumors, and these are already targets for inhibition in cancer chemotherapy. Here, we suggest a different strategy: using the usurped components of the kill switch to activate prodrugs, rather than as targets for inhibition. This strategy is in its infancy, but has the potential to enable more tumor-specific cytotoxicity, which the inhibition strategy generally cannot achieve. Detection of the usurpation of kill switch elements in liquid biopsy analyses enables the collection of information relevant to this new class of tumor biomarkers without the necessity of invasive tissue biopsy

Composition and formulations and their use as nociceptic, anti-anxiolytic and anabolic agents

Composition and formulations comprising a first agent such as folinic acid, pharmaceutically acceptable salts thereof or mixtures thereof, and a second agent(s) such as analgesics, muscle relaxants, mood disorder agents, anti-inflammatories, anti-migraine agents, anti-emetics, diuretics, high protein composites, and the like. The products are suitable as nociceptics and for the treatment of wasting disorders, bulimia, anorexia nervosa, anxiety, irritability and other symptoms associated with Pre Menstrual Syndrome, as well as for administration either in conjunction with steroids or to compensate adenosine depletion and/or bizarre behavior or aggression common in steroid users

Method of treating adenosine depletion

A method of treating adenosine depletion in a subject in need of such treatment is disclosed. The method comprises administering to the subject folinic acid or a pharmaceutically acceptable salt thereof in an amount effective to treat adenosine depletion. A method of treating asthma in a subject in need of such treatment is also disclosed. The method comprises administering to the subject dehydroepiandrosterone, analogs thereof, or pharmaceutically acceptable salts thereof in an amount effective to treat asthma

Low adenosine anti-sense oligonucleotide, compositions, kit and method for treatment of airway disorders associated with bronchoconstriction, lung inflammation, allergy(ies) and surfactant depletion

An in vivo method of selectively delivering a nucleic acid to a target gene or mRNA comprises the topical admistration, e.g. to the respiratory system, of a subject of a therapeutic amount of an oligonucleotide that is antisense to the initiation codon region, coding region, 5' or 3' inton-exon junctions or regions within 2 to 10 nucleotides of the junctions of the target gene, or antisense to a mRNA complementary to the target gene in an amount effective to reach the target polynucleotide and reducing or inhibiting expression. Additionally, a method of treating and adenosine mediated effect is described also utilizing the delivery of antisense and in order to minimize triggering adenosine receptors by their metabolism, the administered oligos have a low content of or are essentially free of adenosine. The agent, composition and formulations are used for prophlactic, preventive and therapeutic treatment of ailments associated with impaired respiration, lung allergies and/or vasoconstriction, inflammation, allergies, allergic rhynitis, asthma, impeded respiration, lung pain, cystic fibrosis and bronchoconstriction

Agent and method for treating disorders associated with cytidine deaminase or deoxycytidine deaminase overexpression

An agent of the chemical formula C.sub.7 N.sub.3 H.sub.8 O.sub.2 R.sup.1 R.sup.2 XX.sup.1, wherein X and X.sup.1 are each independently C or N but not simultaneously, R.sup.1 is lower alkyl, alkenyl or alkynyl, halogen or haloalkyl, and R.sup.2 is H, --N.sub.3 --OH, amino or halogen; or pharmaceutically acceptable salts thereof. A method of treating a disorder associated with the overexpression of cytidine deaminase or deoxycytidine deaminase comprises administering to a subject in need of the treatment a compound of the chemical formula ##STR1## wherein X and X.sub.1 are each independently C or N; R.sup.1 is lower alkyl, lower alkenyl, lower alkynyl, halogen, or haloalkyl; and R.sup.2 H, --N.sub.3, --OH, amino, or halogen; or a pharmaceutically acceptable salt thereof in an amount effective to treat the disorder. Pharmaceutical formulations useful in the method of the present invention are also disclosed

Compositions & formulations with a non-glucocorticoid steroid &/or a ubiquinone & kit for treatment of respiratory & lung disease

A composition comprises as the active agent a Non-glucocorticoid steroid, analogue thereof, a ubiquinone, or their salts, in an amount effective for reducing levels of, or hypersensitivity to, adenosine, increasing levels of lung surfactant or ubiquinone, or for preventing or treating respiratory, lung and cancer diseases. The present treatment is useful for treating asthma, rhinitis, COPD, CF, RDS, pulmonary fibrosis, cancer and other diseases

Composition, formulations & method for prevention & treatment of diseases and conditions associated with bronchoconstriction, allergy(ies) & inflammation

A pharmaceutical composition effective for preventing and alleviating bronchoconstriction, lung allergy(ies) and inflammation comprises a surfactant and an oligonucleotide anti-sense to an adenosine receptor gene, flanking regions or regions bridging the intro/exon borders, analogues which bind thymidine but have low adenosine content or exhibit lower or no adenosine receptor agonist activity, or antisense to the corresponding mRNA, combinations, sales or mixtures thereof, and a carrier, and optionally other therapeutic agents and formulation products. The composition is formulated for administration by a multiplicity of routes, and finds applications in the prevention and treatment of asthma, kidney damage or failure, ARDS, pulmonary vasoconstriction, inflammation, allergies, impeded respiration, respiratory distress syndrome, pain, cystic fibrosis, pulmonary hypertension, pulmonary vasoconstriction, emphysema, chronic obstructive pulmonary disease (COPD), and cancer, to counter the renal damage and failure associated with ischemic conditions and the administration of certain drugs and radio active diagnostic and therapeutic agents, as well as a joint therapy with the administration of adenosine and adenosine-like agents in the treatment of arrhythmias such as SVT and in cardiovascular function tests (stress tests). The present agent(s) is (are) also suitable for administration before, during and after other treatments, including radiation, chemotherapy, antibody therapy, phototherapy and cancer, and other types of surgery

Autoinflammatory Reaction in Dogs Treated for Cancer via G6PD Inhibition

Glucose-6-phosphate dehydrogenase (G6PD) is an oncoprotein that is overexpressed in cancer cells to provide the NADPH required for their increased anabolism. NADPH, sourced from G6PD fuels nucleotide biosynthesis, maintains redox potential of thioredoxin and glutathione and drives the mevalonate pathway that powers many of the basic mechanisms by which cancer cells escape host control. G6PD is thus a target for cancer treatment being addressed by many groups around the world. We have discovered that systemic inhibition of G6PD by high dose dehydroepiandrosterone (DHEA) causes a severe autoinflammatory response in dogs, which does not occur in mice or rats. Since dogs more closely model the human adrenal androgen system than do common laboratory animals, this finding is relevant to the design of G6PD-inhibiting drugs for humans. The autoinflammatory reaction observed closely resembles mevalonate kinase deficiency (MKD), a rare autosomal recessive disease in humans characterized by recurrent febrile attacks, arthralgia, skin rash, and aphthous ulcers of mucocutaneous tissues. In a manner comparable to animal models of MKD, the reconstitution of protein geranylgeranylation blocked the autoinflammatory reaction caused by systemic G6PD inhibition. This autoinflammatory response to systemic G6PD inhibition represents an unexpected result that must be taken into consideration when targeting this oncoprotein

Method of inhibiting carcinogenesis by treatment with dehydroepiandrosterone and analogs thereof

A method of combatting cancer in a subject comprising administering to said subject dehydroepiandrosterone (DHEA) or an analog thereof in an amount effective to combat cancer is disclosed in which heart failure induced by the DHEA or analog thereof is combatted by administering to the subject a ubiquinone, in an amount effective to combat heart failure induced by the DHEA or analog thereof. A prefered DHEA analog for carrying out the invention is 16 alpha-fluoroepiandrosterone, and a preferred ubiquinone for carrying out the invention is Coenzyme Q.sub.10