Enerceutical Mediated Activation Of The Alternative Cellular Energy Pathway In The Therapy Of Infectious Diseases
MARTIN WJ
Institute of Progressive Medicine, Burbank, CA, USA
Background: Stealth adaptation of viruses refers to the loss of the relatively few virus antigens that are normally targeted by the cellular immune system. Consequently, these viruses evade effective recognition by the cellular immune system. Stealth adapted viruses are postulated to be a major cause of human illnesses, especially those with prominent neuropsychiatric features, including autism in children and depression/cognitive disorders in adults. A non-immunological, auxiliary defense mechanism can repair the cytopathic effect (CPE) caused by stealth adapted viruses in tissue cultures. The repair is mediated by particulate, pigmented materials that are typically fluorescent, occasionally magnetic and can show both electron donating and water splitting capacities. Ultraviolet (UV) light evoked fluorescence can commonly be enhanced using various dyes, including neutral red. The materials seemingly provide a non-mitochondria source of cellular energy. Alternative cellular energy (ACE) pigments are detectable in tissues and body fluids of patients with various illnesses. Comparable materials, termed Enerceuticals, are being formulated for potential clinical use in illnesses caused by both stealth adapted and conventional viruses.
Methods: In an ongoing study in patients with autism, paper towels moistened with a particular Enerceutical preparation and neutral red dye, are layered onto a polyethylene sheet that covers parts of the body. The paper towels are rendered fluorescent using UV-A illumination. The patients are observed for skin fluorescence occurring elsewhere on the body and for post-treatment signs of clinical improvement. A similar approach is being used in the therapy of patients with recurrent herpes simplex virus (HSV) infections and with HZV induced post- herpetic neuralgia.
Results: Major clinical improvements, described and updated regularly at www.iminhere.ca, are occurring in autistic patients following 2-5 daily, 30-60 minute sessions using the above protocol. Single therapies are also achieving expedited healing of active HSV and HZV lesions, along with a marked reduction in HSV recurrences and in the severity of HZV associated neuralgia.
Conclusion: Activation of the ACE pathway can provide an effective means of treating illnesses due to both stealth adapted and conventional virus infections.
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How To Implement Pharmaceutical Care In The Curriculum?: The Cuban Pharmacy Education Experiences
MARTINEZ-SANCHEZ AM
Pharmacy Department, University of Oriente, Santiago de Cuba - Cuba
Background: Pharmacy schools across Cuba have been charged to ensure their students are adequately skilled in the principles and practices of pharmaceutical care. Despite this mandate, a large percentage of students experience insufficient opportunities to practice the activities, tasks and processes essential to pharmaceutical care. This paper presents a point of view about how pharmaceutical care should be incorporated in the curricula for improving the confidence and skills of pharmacists responding to pharmaceutical care practice taking into consideration the ethical dimension of this concept. At the same time, some ideas about this topic are presented, taking as reference, the Cuban experience in pharmaceutical care education, supported in the worldwide recognition of the Cuban Higher Education.
Methods: theorical research methods were applied, such as analysis and synthesis, and statistical method.
Results: The theoretical contribution of this research lies in offering a didactic model to implement pharmaceutical care in to the curricula, the knowledge, abilities and professional values are considered as a system, to provide all the principles and practices components for the pharmaceutical care in the pharmacy curriculum.
Conclusions:Many methods to be used to teach student to provide pharmaceutical care, but it is important to understand that the clinical pharmacy method as logical expression of pharmaceutical care process should be taught; taking into account that, the professional method acquires during the teaching – learning process a greater importance than answering a specific problem. The scientific facts and data learnt today can become obsolete or even not be accepted in a near future. On the contrary, those pharmacists who can identify and solve their patient’s drugs - related - problems by applying a reasonable method will be able to adjust themselves to the continuous and speedy evolution of scientific knowledge so as to scientifically contribute to a better health and their patient’s quality of life.
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New Horizons In Respiratory Allergy Therapy And “Magic Bullets”: Could It Be Possible To Include Antiprotozoal Drugs?
MARTÍNEZ-GIRÓN R
Protozoal Respiratory Pathology Research Unit, Fundación INCLINICA, Oviedo, Spain
Background: The allergic diseases that affect the respiratory pathways have reached epidemic proportions in recent decades. For many years now, a close relationship has been established between these diseases and products corresponding to certain arthropods such as mites and cockroaches. Although it is ten years since the presence of certain protozoa in the sputa of asthma patients was first described, observation of the existence of protozoa in the intestinal extracts of dust mites, as well as of other protozoan forms in the intestine of cockroaches, has recently led us to consider a possible etiopathogenic role in the development of respiratory allergy. This role may be reinforced if we bear in mind that the inhalation of faecal particles of such arthropods may introduce pathogens into the respiratory pathways. This suggests to us that the use of antiprotozoal drugs may be effective in the treatment of diseases such as bronchial asthma and allergic rhinitis.
Methods: To review the publications available in different fields of medicine that refers uncommon and unknown kinds of protozoa that may affect the human airways.The literature review was identified trough electronic data bases such as MEDLINE, EMBASE, and the COCHRANE DATABASE of SYSTEMATIC REVIEWS. Peer-reviewed publications in English, French, and Spanish language, and English-language abstracts of non-English papers, identified in our research, were included.
Results: Uncommon multiflagellated protozoa belonging principally to Phylum Sarcomastigophora, Order Hypermastigida, and observed in intestinal extracts of mites and cockroaches, also have been found in human respiratory airways secretions, especially in patients with respiratory allergy (bronchial asthma and allergic rhinitis) and/or immunosuppression status (AIDS, transplants, cancer, etc.).
Conclusions: It is evident that, despite great efforts and new therapeutic approaches, allergic respiratory diseases continue to be on the increase. Until now, only the possible role of certain microorganisms (viruses, bacteria and fungi) has been taken into account in the development of these diseases. The existence of uncommon protozoa related with arthropods such as dust mites and cockroaches may open up new etiopathogenic, therapeutic and preventive perspectives.
References:
Ribas A, Mosquera JA. Ameboflagellates in bronchial asthma. Acta Cytol 1998; 42: 685-690.
Ribas A, Martínez-Girón R. Protozoal forms in house dust mites and respiratory allergy. Allergy Asthma Proc 2006; 27: 347-349.
Martínez-Girón R, Ribas A. Asthma, cockroaches and protozoal forms: chance or not chance? Ann Allergy Asthma Immunol 2006; 97: 818-819.
Martínez-Girón R, van Woerden HC, Ribas-Barceló A. Could inhaled mite faeces introduce pathogens to the lungs? Microbes Infect 2008; 10: 452-453.
Martínez-Giron R, Doganci L, Ribas A. From the 19th century to the 21st, an old dilemma: Ciliocytophthoria, multiflagellated protozoa, or both? Diagn Cytopathol 2008 36: 609-611.
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Optimizing A Therapeutic With Nsaids: Intelligent Design For Delivery Systems
MARTINS LOPES C1, COELHO PB1, SANTOS D2, OLIVEIRA R1, SOUTO E1
1Faculty of Health Sciences, FCS, Fernando Pessoa University, Porto, Portugal; 2 Faculty of Pharmacy, Porto University, Porto, Portugal
Background: There is a wide approach to modulate drug release with the objective of optimizing therapy. The type of drug will define the type of release to achieve. The NSAIDs are used in anti inflammatory diseases, so it would be desirable to develop a quick/slow delivery system to alleviate rapidly the painful symptoms and to avoid repeated administrations. Aims: 1) To develop biphasic delivery systems based on compressed or encapsulated mini tablets 2) To study the dosage regimen flexibility.
Methods: Prolonged-release component: The mini tablets contained either HPMC or EC as controlling agents and ibuprofen as a model drug. Mini-tablets, 12 mg and 2.5 mm, were prepared by direct compression in an instrumented mechanical press machine. Fast-release component: The filling of the void spaces between mini-tablets was formulated to produce an immediate release. The composition was identical for all formulations and contained the immediate release drug dose, microcrystalline cellulose and sodium croscarmellose. Compressed mini-tablets systems: The die of the tabletting machine was progressively filled with the weighed amounts of the fast release component and the mini-tablets prior to compression. Tablets were prepared by direct compression. Encapsulated mini-tablets systems: These systems were prepared by encapsulating the weighed amounts of the fast release component and mini-tablets in a hard capsule.
The dosage regimen flexibility was studied by combination of a different number of mini-tablets (prolonged release component) and a different dose of the drug (fast release component).
Results: The biphasic delivery systems were characterized by an initial rapid release, corresponding to the drug release contained in the powder component, followed by a period of slow release, corresponding to the drug release of mini-tablets. The release profile was dependent on the number and/or composition of subunits, making up the drug sustained dose. After the disintegration of the biphasic systems, the HPMC subunits were able to release a second dose fraction in a prolonged time (≈ 7h) at a constant rate and with an identical dissolution profile to the original mini-tablets. In the case of biphasic EC mini-tablets systems, the releasing of fast component disturbed the drug diffusion mechanism.
Conclusions: 1) Biphasic quick/slow preparations of ibuprofen were developed by compressing or encapsulating a combination of powder and mini-tablets. 2) The proposed biphasic delivery devices show flexibility in the modulation of the delivery program.
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Biomedical Application Of Electron Spin Resonance (ESR) Spectroscopy Using Blood-Brain-Barrier (BBB) Permeable Nitroxyl Spin Probe
MASAICHI-CHANG-IL L
Department of Clinical Care Medicine, Division of Pharmacology & ESR Laboratories, Kanagawa Dental College, Yokosuka, Japan
Background: Oxidative stress induced by reactive oxygen species (ROS) are associated with the alterations under pathophysiological conditions, and particularly in brain ischemia, brain tumor, and neurodegenerative diseases. Therefore, we need to understand the physiological and pathophysiological role of oxidative stress induced by ROS in the brain.
Methods: This study examined two nitroxyl compounds, BBB-permeable 3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine-1-oxyl (MC-PROXYL) and BBB-impermeable carbamoyl-PROXYL, as spin probes for evalution oxidative stress in the brain using by in vivo ESR or ESR imaging technique. Preliminary comparisons were made by in vivo ESR or ESR imaging of the heads of live mice and isolated rat brains using MC-PROXYL and the carbamoyl-PROXYL. These methods were also applied for the in vivo ESR or ESR imaging of isolated brains from spontaneously hypertensive rat (SHR) and stroke-prone SHR (SHRSP), which were well known high oxidative rodent model.
Results: The results showed that MC-PROXYL, but not carbamoyl-PROXYL, was widely distributed in the brain. The rapid decay of 2D ESR images of MC-PROXYL in isolated SHR-brain and SHRSP-brain was observed, compared to normotensive Wistar-Kyoto rats (WKYs), using the ESR imaging system. Furthermore, we provided evidence that the decay rate of MC-PROXYL in the head region was faster in live SHRs and SHRSPs than in live WKYs, by using in vivo ESR non-invasively. Taken together, the high oxidative stress sustained by ROS in SHR and SHRSPs may cause the alteration of MC-PROXYL metabolism in the brain.
Conclusions: Our results suggest that in vivo ESR could be applied to the assessment of antioxidant effects on oxidative stress in the brain in rodent disease models, such as the SHR and SHRSP. Further advances in the instrumentation of ESR imaging and would make this technology even more promising for the non-invasive diagnosis of oxidative stress induced-brain diseases in vivo. Furthermore, after screening test of drugs or foods using in vivo ESR technique, we’ll be able to develop and find drugs or foods with novel antioxidant property in the near future.
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Nobel Prize Winners In Medicine And Physiology
MAŠIĆ I
Medical faculty, University of Sarajevo, B&H, Sarajevo, Bosnia and Herzegovina
The Nobel Prize in Physiology or Medicine is awarded once a year by the Swedish Karolinska Institute. It is one of the five Nobel Prizes established by the will of Alfred Nobel in 1895, awarded for outstanding contributions in physics, chemistry, literature, peace, and physiology or medicine since 1901.
The first Nobel Prize in Physiology or Medicine was awarded in 1901 to Emil Adolf von Behring, a German, “for his work on serum therapy, especially its application against diphtheria, by which he has opened a new road in the domain of medical science and thereby placed in the hands of the physician a victorious weapon against illness and deaths.” This award is administered by the Nobel Foundation and widely regarded as the most prestigious award that a scientist can receive in these fields.
It is presented in Stockholm at an annual ceremony on December 10, the anniversary of Nobel’s death. “The highlight of the Nobel Prize Award Ceremony in Stockholm is when each Nobel Laureate steps forward to receive the prize from the hands of His Majesty the King of Sweden. ... Under the eyes of a watching world, the Nobel Laureate receives three things: a diploma, a medal and a document confirming the prize amount” (“What the Nobel Laureates Receive”). In 2007 the Nobel Prize in Physiology or Medicine was awarded to Mario Capecchi (of Italy), Sir Martin Evans (of the United Kingdom), and Oliver Smithies (of the United Kingdom and the United States), “for their discoveries for introducing specific gene modifications in mice by the use of embryonic stem cells”; they share the prize amount of 10,000,000 SEK (slightly more than €1 million, or US$1.4 million). The front side of “The medal of the Nobel Assembly at the Karolinska Institute” provides the same profile of Alfred Nobel depicted on the medals for Physics, Chemistry, and Literature; its reverse side “represents the Genius of Medicine holding an open book in her lap, collecting the water pouring out from a rock in order to quench a sick girl’s thirst” (“The Nobel Prize Medals”).
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Effect Of Formulations On Clopidogrel Bioactivity And Bioavailability In Vivo
MASRI MA, JAALOUK G, RIZK S, BARBOUCH H, ATTIA M
Transmedical Research Institute Beirut, Lebanon
Clopidogrel hydrogen sulphate is antiplatelet agent approved for use in secondary prevention of heart attacks and stroke. Although millions of cardiac patients are benefiting from Clopidogrel treatment, however, nearly 5% of the patients are Clopidogrel “nonresponsive”.
The pharmacokinetics parameters of Clopidogrel, under fasting conditions, are conflicting as to the maximum concentration achieved following the dose (Cmax) with a range of 1.2 ng/ml to 9 ng/ml and a time to maximum concentration (Tmax) of 1 hour to 2.5 hours.
These results are more controversial under feed conditions with studies showing no effect of food on the pharmacokinetics of Clopidogrel in Caucasians while studies in East Indian population demonstrated a significant influence of food. In these studies Tmax increased from 2.5 hours to 5 hours and the Cmax was increased by 5 folds. Moreover, there is a direct effect of genetics on the absorption and thereby active metabolite formation which are diminished by P-gp-mediated efflux and are influenced by the MDR1 C3435T genotype. We have performed a comparative study on the bioavailability and correlated that with in vivo bioactivity, as measured by inhibition of platelet aggregation, of two formulation of Clopidogrel (Plavix manufactured by Aventis France vs Pidogrel manufactured by Medis Tunisia). The study was balanced, randomized, two-treatment, two-period, single dose, crossover, in 36 (17 females and 19 males) healthy, adult, human subjects, with a wash out period of 7 days.
The subjects received a single dose of 75 mg following a 12 hour fast but with a standardized breakfast 2 hours following the dose. Clopidogrel blood levels were determined using an HPLC on samples obtained at: Pre-dose and at, 30, 60, 75, 90, 120, 240, 360, 480, 600, 720 and 1440 minutes following drug administration. The bioactivity studies (inhibition of platelet aggregation was performed on the samples collected at 0,120,360,600 and 1440 minutes. The bioactivity was determined using two methods: reduction of surface coverage (using the impact-R instrument from DiaMed Switzerland) and the platelet aggregation time using the Behring coagulation time (BCT) from Dade Behring. The Cmax, Tmax were 8.78 ng/ml, and 2 hours for Pidogrel vs 9.16 ng/ml and 2 hours for Plavix respectively. For both formulations there was an increase (not significant) in platelet aggregation from base line at 2 hours past the dose. Platelets aggregation was inhibited equally by the two products at six hours post dose as measured by the two methods. The platelets of 2 subjects were resistance to the effect of both formulations. Our results indicate that both formulations have comparable bioavailability and bioactivity under the conditions tested. It is recommended to determine the Clopidogrel bioactivity prior to and six hour post the does for all the patients who need the Clopidogrel therapy.
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Integrated 'OMIC' Analyses Of The Rat Brain: Novel Biomarker Candidates For Mental Disorders And Stress
MASUO Y, HIRANO M, SHIBATO J, RAKWAL R
National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan
Background: It has been well known that stress may cause mental disorders. However, the process from stress to disorders is not clear yet. Aims: 1) To clarify the effects of several kinds of stress on the brain. 2) To understand mechanisms of animal models for mental disorders, such as depression and developmental disorders. 3) To determine multiple stress markers that may play important roles in mental disorders.
Methods: This study included 280 rats. We prepared animal models for attention-deficit hyperactivity disorder (ADHD) and depression. For ADHD, male rats at 5 days of age received intracisternal injection of 6-hydroxydopamine (6-OHDA) or environmental chemicals. Male congenic wiggling (Wig) rats were generated using Long-Evans and Wistar strains. For depression, adult male rats were exposed to the stress, such as immobility or water. Moreover, we examined the effects of continious light, gamma knife treatment and alcohol drinking. These brains were analyzed by transcriptomics using DNA microarray and proteomics with two-dimensional gel electrophoresis followed by mass spectrometry. In some experiments, we performed metabolomics by NMR.
Results: A deficit in the development of dopamine (DA) neurons caused behavioral hyperactivity similarly to ADHD. Alterations in the expression of genes and proteins in brain regions showed variation among environmental chemicals and differed from those of 6-OHDA-injected and Wig rats. With these techniques, we found stress marker candidates that were similarly altered by immobility, water, and continuous light. Among these, we observed that coffee bean aroma attenuated the effects of water stress (sleep deprivation). Moreover, several stress marker candidates were found after gamma knife treatment and alcohol drinking.
Conclusions: 1) Deficient development of DA neurons may underlie motor hyperactivity, and additional factors may be altered in Wig rats and animals exposed to environmental chemicals, which may reflect different types of ADHD patients. 2) Different kinds of stress that may cause depression altered similar potential biomarkers in the brain. 3) OMIC tools will be useful to study possible alterations in the expression of multiple factors in the brain.
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