Factors that positively or negatively mediate the effects of age on working memory across the adult life span.

Working memory abilities significantly decrease with advancing age; hence, the search for factors that may increase or mitigate this decline is critical. Several factors have been identified that influence working memory; however, their effects have been mainly assessed separately and rarely together with other factors in the same sample. We examined 120 variables to search for factors that jointly act as mediators of working memory decay across the adult life span. A sample of 1652 healthy adults was assessed in spatial and verbal working memory domains. Structural equation modeling analyses were conducted to search for potential mediators that intervened between age and working memory. Only 14 and 10 variables reliably mediated spatial and verbal working memory, respectively. Factors from several domains remained in the models, such as individual characteristics, physiological traits, consumption habits, and regular activities. These factors are sufficiently powerful to influence working memory decline when they jointly interact, as in everyday living.

Mediators of episodic memory decay across the adult life span.

The ability to remember the details of our own experiences declines gradually as we get old. The reason for this decay has been attributed to several factors besides age, such as education, nutrient intake and health status. However, the influence of these factors has mainly been examined individually and rarely together. Here we identify those factors that jointly act as mediators of episodic memory decay across the adult life span. We examined source memory in a lifespan sample of 1557 healthy adults. A total of 70 physical, biological and lifestyle variables were measured and introduced into a structural equation model as potential mediators that intervene between age and source memory. Only 14 mediator variables reliably mediated source memory decay; notably, eight of these variables have an effect on the cardiovascular system. The model unequivocally highlights that the mediators that may impair cardiovascular functioning also impact brain resources involved in episodic memory. We identified the factors that are relevant to episodic memory decline when they interact together as occurs in real life.

Role of epidermal dendritic cells in drug-induced cutaneous adverse reactions.

Drug-induced adverse reactions (ADR) include any undesirable pharmacological effect that occurs following drug administration at therapeutic doses. The appearance of ADR significantly limits the use of drugs in as much as their clinical symptoms may range from very mild discomfort such as cutaneous rash, up to very severe, or even fatal tissue necrolysis such as the Stevens Johnson syndrome.One of the most frequently involved organ during ADR is the skin. Drug-induced cutaneous reactions (CDR) incidence is variable but they may appear in 2-3% of ambulatory patients, and it may increase to 10-15% when patients are hospitalized, or even be as high as 60% when co morbidity includes the presence of virus, bacteria, or parasites.Due to the fact that skin is one of the organs most frequently involved in ADR, in this work we analyze and propose a mechanism by which epidermal dendritic cells operating as the sentinels of the skin neuro-immune-endocrine system may contribute to CDR via either immunogenic or tolerogenic immune responses towards drugs, whenever they are administered topic or systemically.

Oral calcium administration attenuates thrombocytopenia in patients with dengue fever. Report of a pilot study.

Global climate change is one of the instigating and contributing factors for epidemic outbreaks of infectious diseases in human populations. In the years 2003 to 2005 the city of Tampico, in the northern state of Tamaulipas, Mexico, experienced recurrent outbreaks of dengue virus infections (DV) and the resulting dengue fever (DF). One of the hallmark symptoms of DF, which appears to worsen as the environmental temperature increases, is thrombocytopenia. In as much as it is a hallmark for hemorrhagic manifestations, thrombocytopenia is a useful sign to monitor the course of infected patients. Extracellular calcium (Ca2+ o) plays a key role in blood clotting; its chelation in vitro with ethylenediaminetetracetic acid (EDTA) or citrate prevents clotting, while exogenous recalcification of plasma leads to shortening of clotting time. In vivo, Ca2+ o is essential for platelet function and for the regulation of the immune response. In this work we report a significant increase (p<0.05) in the number of blood platelets of patients with clinical signs and symptoms of DF following oral administration of calcium carbonate (CAL, 1.2 to 1.8 g/day; n=10) when compared with a control group (CTL, n=10): 89 (46-132) versus 206 (155-257). Data expressed as mean value (95% confidence interval, C.I.) for x1000 cells/mm3. CAL also improved overall clinical condition and reduced by 36 % the duration of signs and symptoms of DF: 6.7-11.3 days, versus 11.5-16.6 days (95 % C.I., p<0.05) when compared with CTL patients. The possible mechanism of calcium attenuated thrombocytopenia and clinical improvement is discussed.

Clinical efficacy of a petroleum-derived product (Larimsh) used as compassionate treatment in patients with terminal prostate cancer.

Treatment of a light fraction of petroleum treated by metallic catalysis results in a liquid mixture of low molecular weight compounds named LarimshTM (LR). Acute and chronic topical treatment of mice with LR (85 days with 0.1 to 1 mL/animal) indicated no signs of toxicity other than a non dose-dependent, reversible alopecia appearing by the 4th week of topical application. Alopecia completely reversed 2 weeks after treatment withdrawal. Acute oral LR (0.001 to 1 mL; the lowest doses diluted in corn oil as vehicle) gave an estimated LD50 of 21 g/kg (C.I. 95 %: 10.94-41.2 g/kg. LR density = 0.867 g/mL). The antineoplastic action of LR was observed using combined oral and topical treatments in mice; inoculated with a lymphoid leukemia cell line in ascitic phase (International Registry L5178Y); and in terminal patients with prostate cancer (TPCA)--who agreed to receive LR as a compassionate treatment. The survival time for mice was significantly increased when compared with non-treated inoculated mice (51 +/- 2 versus 38 +/- 2 days, p < 0.05, mean +/- SD, N = 6 per group). In 15 patients, LR treatment for 5.5 months (C.I. 95 %: 2.9 to 8.0 months) significantly increased the expected survival time diagnosed to TPCA by their treating physicians (C.I. 95 %: 2.2 to 5.4 versus 12.6 to 41.2 months, p < 0.05) which occurred concomitantly with a significant reduction of blood levels of total prostatic antigen (average 94.5%, range: 67.3 to 99.9%). A theoretical proposal is advanced as a likely explanation of LR actions.

Drug administration is an essential clinical competence.

Quotidian clinical practice implies at least four essential activities: i) integration of diagnosis; ii) design of the therapeutic regimen; iii) following up therapeutic outcomes; and, iv) keeping updated on medical knowledge. The therapeutic regimen may include the use of drugs among other forms of treatment. A competent clinician is expected to be knowledgeable, skillful, dutiful and altruistic when deciding to use drugs. In this work, drug administration is proposed to be redefined as an ssential clinical competence that integrates basic medical pharmacology knowledge (BMPK) along with pharmacotherapy's abilities and skills. Medical students should learn and become efficient in deciding what drugs are useful for specific patients; how drug(s) should be administered, i.e., dosing and duration of treatment; when drugs should be withdrawn or not used; and, how physicians are to keep updated for a sound balance when deciding between old or new drugs. Medical Pharmacology texts review these topics in the sections of clinical pharmacology, clinical pharmacokinetics, pharmacotherapy and pharmacoeconomics. However, an integrated view on how BMPK relates to their clinical application is not clearly stated. By the same token, legal and ethical aspects of drug administration are narrowed to prescription writing skills, either for the patient or for the clinical file; thus, attenuating the appraisal of the impact on therapeutic adherence of physicians' communication skills, as well as availability and/or accessibility of recommended drugs. These issues are obviously related to therapeutic outcome but their integrated articulation occurs only if drug administration is considered as an essential clinical competence.

Participation of epidermal langerhans cells in human pathology and their potential as targets for drug development: a review of literature.

Langerhans cells (LC) are antigen presenting cells of the epidermis originated from bone marrow progenitors that arrive into the epidermis through the blood vessels LC are also referred to as dendritic cells. In the presence of antigens LC become activated and migrate from the skin to the lymph nodes where they induce T cells responses, therefore, LC function as sentinels of the epidermis and constitute, in part the Skin Immune System (SIS). LC have been implicated in the pathogenesis and pathophysiology of diverse diseases such as atopic dermatitis, alopecia areata, human immunodeficiency virus infection (HIV) and melanoma, among others. The aim of this review is to draw the attention of pharmacologists towards LC as targets for drug action and drug development due to their immunesurveillance function. LC modulate the SIS as an endogenous mechanism of defense against many infectious agents, xenobiotics, and for the treatment of cancer, infections, and autoimmune diseases. A review of the literature on LC is presented here giving emphasis to LC cell cycle and cellular and molecular characteristics, LC possible role in human pathologies, and LC therapeutic potential.

Effects of single administration of diethylstilbestrol on murine langerhans cells.

Diethylstilbestrol (DES) is a synthetic compound with potent estrogenic actions useful in the treatment of prostate carcinoma despite the fact that it can also induce some forms of neoplasia. Both effects are thought to be related to its estrogenic actions and very little attention has been focused on the possible effect of DES on the immune response. Skin is the largest organ of the body and constitutes the first line of defense against xenobiotics. The Skin Immune System (SIS) has become the center of attention of research for the development of new therapeutic approaches for neoplasic diseases. Langerhans cells (LC), as an element of SIS, are "professional" antigen presenting cells resident in the skin that participate in the immune response associated with tolerance and acquired immunity to antigens. Hence in this work we studied the effect of DES on LC of murine skin as a model to analyze the possible effect of DES on the immune response. Male CD-1 mice (20 to 35 g body weight) were treated topically (TO) or subcutaneously (SC) with DES (10 and 100 mg/kg, dissolved in ethanol) and sacrificed at 12, 84 and 228 hr. LC were quantified in the ear skin of mice using both an enzymatic histochemical technique to demonstrate ATP-ase activity; and an indirect immunohistochemical assay for detecting class II molecules of the major histocompatibility complex (MHC-II). DES induced a significant time- and dose- dependent reduction in the number of LC (P < 0.05). Data presented here suggest that estrogens may exert a modulatory action on LC.

Selection of information resources for education in medical pharmacology.

Pharmacology is the foundation science of medical pharmacotherapy. Education in medical pharmacology (EP) requires the use of information resources (IR) to meet the challenge of the continuous introduction of new drugs and new educational, didactic and pedagogical theories to enhance knowledge. Hence criteria for selecting bibliographic material for EP should be clearly outlined and implemented. In this work we present a method to select IR for EP based on systems theory and focusing on the factors determining: (a) the integration of a list of recommended IR for EP; (b) the design of the acquisition list for faculty and students work; (c) the overall organization of the resources available for its optimal use and benefit in the educational process; and (d) a general strategy for assessing the impact of the bibliographic infrastructure. The proposal is based on information from: (i) lists of recommended readings in the academic program of the Pharmacology course given at the School of Medicine of UNAM in the last 30 years; (ii) the extent of discipline development measured by two indexes derived from the contents of Goodman and Gilman's "Pharmacological Basis of Therapeutics" (G & G); (iii) the number of texts currently found in the collection of FM-UNAM which are classified in the section of Pharmacology using the Library of Congress Classification System (LCCS); and (iv) the comparison of academic versus standardized classification of pharmacology topics, such as Medical Subject Heading (MESH) and LCCS The importance of this proposal relates to its usefulness for EP and for other medical disciplines.