Immunity & Ageing - Latest Comments

About an error in the total cell count

Yoshifumi Kotani — 2012-05-08T10:44:23Z

There was an error in the total cell count of the ingested strain, b240.
The correct count is 2 × 10^9 cells, not 4 × 10^9 cells.
This alteration to our data has not led to any changes in the published results, and our conclusions remain unaltered.

Melatonin Origin And Function

Dov Henis — 2009-02-03T16:30:32Z

Beyond Darwin 200 Melatonin Switches On Mostly Intercell Maintenance Wake up. Re-think-plan-do-assess Epigenetics, Sleep And Melatonin works. A. "Epigenetics reveals unexpected, and some identical, results" http://www.sciencenews.org/view/generic/id/40060/title/Epigenetics_reveals_unexpected%2C_and_some_identical%2C_results One study finds tissue-specific methylation signatures in the genome; another a similarity between identical twins in DNA’s chemical tagging. I humbly suggest : Re-think-plan-do-assess Epigenetics Works, founded on scientific conception that genes and genomes are organisms. B. "Sleep, Melatonin, Cancers And Beyond Darwin 200" http://www.the-scientist.com/community/posts/list/100/122.page#1412 I humbly suggest: Re-think-plan-do-assess works, founded on scientific conception that genes and genomes are organisms. C. Apparent functional aspects of melatonin http://cogweb.ucla.edu/ep/Neurology.html#Melatonin Melatonin is a hormone secreted by the human pineal gland during night-time darkness, and it is now being marketed in the US as a nutritional supplement. The hormone is an indoleamine compound derived from the amino acid *tryptophan, with *serotonin as an intermediate precursor. 1) The most important role of melatonin in all species is to provide a hormonal signal of night-time darkness. The secretion of the hormone is tightly controlled by the *circadian pacemaker. 2) Melatonin is a phylogenetically ancient hormone, found even in some single-cell organisms and in some plants. 3) At the cellular level, melatonin receptors are members of the superfamily of *G protein-coupled receptors...Activation of these receptors inhibits *cyclic AMP production by the enzyme adenylyl cyclase. cAMP (cyclic AMP) acts as an intracellular hormone (i.e., a chemical messenger). Cyclic AMP is derived from ATP in a reaction catalyzed by the enzyme adenylyl cyclase (also called adenyl cyclase and adenylate cyclase). I humbly suggest: Melatonin, the phylogenetically ancient hormone, was evolved by the genome during the early single-cells eons when they evolved community life cultures and graduated from sunlight-only to metabolism-too energy production. Melatonin's role was to signal that the genes are asleep, their functional activities are shut off, and it is time for the security and maintenance crews to do their tasks, especially to clean up the intercell environment, for keeping the community of cells in proper state. D. It all adds up to: Gene: a primal Earth's organism. (1st stratum organism) Genome: a multigenes organism consisting of a cooperative commune of its member genes. (2nd stratum organism) "Life's Manifest" http://www.the-scientist.com/community/posts/list/112.page#578 Dov Henis (Comments From The 22nd Century) http://blog.360.yahoo.com/blog-P81pQcU1dLBbHgtjQjxG_Q--?cq=1

Bedside Evaluation endothelial Function in Hypertensives.

Sergio Stagnaro — 2008-08-18T16:05:28Z

I find the paper fascinating and interesting. In addition, Authors’s data agree with my clinical results. The endothelium is notoriously the main regulator of vascular wall homeostasis. Physiologically, endothelial cells maintain a relaxed vascular tone, physiological chaotic movements of both macro- and micro-vessels (2, 3), and low levels of oxidative stress (eNO is a radical!), in part by releasing mediators, including NO, prostacyclin (PGI2), and endothelin (ET-1), and controlling local angiotensin II activity. In addition, the endothelium actively regulates vascular permeability to plasma constituents, platelet and leukocyte adhesion and aggregation, and thrombosis. This state of balanced endothelial regulation of blood vessel function is, however, altered by a number of conditions. Thus, in response to a variety of noxious stimuli, the endothelium undergoes a phenotypic modulation to a nonadaptive state, commonly termed "endothelial dysfunction," characterized by loss or dysregulation of homeostatic mechanisms operative in healthy endothelial cells. This pathophysiological condition is associated with increased expression of adhesion molecules, increased synthesis of proinflammatory and prothrombotic factors, increased oxidative stress, and abnormal modulation of vascular tone, which may lead to different functional manifestations, including impaired endothelium-dependent vasodilation1).

Based on my 52-year-long clinical experience (See www.semeioticabiofisica.it), I state that the evaluation of endothelial function, in every biological system, is realized nowadays also clinically with a simple stethoscope, thanks to Quantum Biophysical Semeiotics (2-10)(www.semeioticabiofisica.it). In fact, among different techniques to evaluate the endothelium functional capacity, that depend on the amount of “radical” NO produced and the vasoactive effects, nowadays there are biophysical-semeiotic methods, applicable on very large scale in a few minutes, even under stress tests. In fact, doctors may assess the intensity of endothelial cell “radical” NO synthesis in order to recognize both artery alteration and ALL other disorders, in simple way (1-5). The percentage of vasodilation immediately after Valsalva’s Manoeuvre, confronting it with the basal value, represents the endothelial functional capacity, that is in relation to the local parenchymal cell functions, according to my Angiobiopathy theory, which complete that of Tischendorf's Angiobiotopy (11). Taking into account that shear stress is one of the most important stimulants for the synthesis and release of “radical” NO, the non invasive technique most often used is the transient flow-modulate “endothelium-dependent” post-ischemic vasodilatation, performed on conductance arteries such as the brachial, radial or femoral arteries. Certainly shear-stress stimulates e-NO synthesis in healthy individual, as allows me to state Biophysical Semeiotics (1-5, 8-10). In addition doctors gather a lot of other information, e.g., after drugs administration (4-8). In fact, such as vasodilatation is compared with the vasodilatation produced by drugs that are NO donors, such as nitroglycerine, called “endothelium independent”. The vasodilatation is quantified by measuring the arterial diameter with high resolution ultrasonography. Laser-Doppler techniques are now starting to be used that also consider tissue perfusion. One must admitt that such as methods cannot be applied neither in apparently "healthy" individual in order to perform primary prevention, neither on very large scale even in diseased subjects. All that accounts for the reason that Microcirculation and Clinical Microangiology under both physiological and pathological conditions, are scarsely known by physicians all around the world, also at universities, unfortunately.

Finally, thanks to Quantum Biophysical Semeiotics, as well as the unknown knowledge of non local realm in biological systems beside the local realm, I recently demonstrated (12-15), doctors are able in 1 second to bedside exclude macro- and micro-vessels alteration: in health, “intense” digital pressure, applied upon an artery do not bring about simultaneously aspecific gastric reflex, whereas such as reflex appears in presence of whatever vascular disorder Inherited Real Risk in individuals involved by well-defined Biophysical-Semeiotic Constitutions (12-14)

References

1) Barac A; Campia U.; Panza J A. Methods for Evaluating Endothelial Function in Humans. Hypertension. 2007;49:748

2). Stagnaro-Neri M., Stagnaro S. Introduzione alla Semeiotica Biofisica. Il Terreno Oncologico. Travel Factory, Roma, 2004. http://www.travelfactory.it

3) . Stagnaro-Neri M., Stagnaro S., Semeiotica Biofisica: valutazione della compliance arteriosa e delle resistenze arteriose periferiche. Atti del XVII Cong. Naz. Soc. Ital. Studio Microcircolazione, Firenze Ott. 1995, Biblioteca Scient. Scuola Sanità Militare, 2, 93, 1995.

4) Stagnaro-Neri M., Stagnaro S., Semeiotica Biofisica: valutazione clinica del picco precoce della secrezione insulinica di base e dopo stimolazione tiroidea, surrenalica, con glucagone endogeno e dopo attivazione del sistema renina-angiotesina circolante e tessutale – Acta Med. Medit. 13, 99, 1997.

5) Stagnaro-Neri M., Stagnaro S., Semeiotica Biofisica: la manovra di Ferrero-Marigo nella diagnosi clinica della iperinsulinemia-insulino resistenza. Acta Med. Medit. 13, 125, 1997.

6) Stagnaro-Neri M., Stagnaro S., Sindrome di Reaven, classica e variante, in evoluzione diabetica. Il ruolo della Carnitina nella prevenzione del diabete mellito. Il Cuore. 6, 617 , 1993[Medline]

7) Stagnaro Sergio Endothelial cell function can ameliorate under safer drugs, such as Melatonin-Adenosine. BMC Cardiovascular disorders, 10 October 2004. http://www.biomedcentral.com/1471-2261/4/4/comments

8) Stagnaro S., Percussione Ascoltata degli Attacchi Ischemici Transitori. Ruolo dei Potenziali Cerebrali Evocati. Min. Med. 76, 1211, 1985 [Medline]

9) Stagnaro-Neri M., Stagnaro S., La sindrome percusso-ascoltatoria da carenza di Carnitina. Clin. Ter. 145, 135, 1994 [Medline]

10) Stagnaro-Neri M., Stagnaro S., Sindrome di Reaven, classica e variante, in evoluzione diabetica. Il ruolo della Carnitina nella prevenzione del diabete mellito. Il Cuore. 6, 617 [Medline]

11) Stagnaro Sergio. Role of Coronary Endoarterial Blocking Devices in Myocardial Preconditioning - c007i. Lecture, V Virtual International Congress of Cardiology. http://www.fac.org.ar/qcvc/llave/c007i/stagnaros.php 2007

12) Stagnaro Sergio e Paolo Manzelli. Semeiotica Biofisica: Realtà non-locale in Biologia. Dicembre 2007, www.ilpungolo.com, http://www.ilpungolo.com/leggi-tutto.asp?IDS=13&NWS=NWS5217

13) Stagnaro Sergio e Paolo Manzelli. Semeiotica Biofisica Quantistica. http://www.ilpungolo.com/leggi-tutto.asp?IDS=13&NWS=NWS5243

14) Stagnaro Sergio. Non Local Realm. Response to Selection for Social Signalling Drives the Evolution of Chameleon Colour Change. (01 February 2008). www.plos.com, http://biology.plosjournals.org/perlserv/?request=read-response&doi=10.1371/journal.pbio.0060025

Augmenting immune system activiti in aging is really complex.

Sergio Stagnaro — 2008-03-17T06:37:11Z

Editors,

This paper is really interesting, paying attention to the most outstanding problems of vaccination in aging people. However, NOT all aged individuals are equal, in the sense that, e.g., melatonine deficiency as well as Co Q10 deficiency syndrome is present in some but not all (1-5).Melatonine, among a lot of other actions, stimulates immunesystem, and Ubidecarenone is a potente scavenger of free radicals, as Melatonine.

In my opinion, bedside biophysical-semeiotic diagnosis of Co Q10 deficincy syndrome, I described earlier (1-4), could be very helpful in risk stratification to predict absence of benefical effect after vaccination in Older Adults. In fact, I have demonstrated that doctors can clinically recognize subjects involved by Ubidecarenone deficiency, even initial and symptomless, causing damage of tissues due to the increase levels of free radicals (1-4). Moreover, in my 52-year-long clinical experience, such as diagnosis, made for the first time clinically, proved to be really efficaious and reliable in avoiding dangerous administration of statine to individuals without clinical sintomatology, but involved by ubidecarenone deficiency, notoriously worsened by anti-cholesterolemic drugs. In addition, physicians are able to recognize since birth whatever inherited biophysical-semeiotic Real Risk, including oincological and diabetic one (5, 6, 7), based on microvascular remodelling, characterized by newborn-pathological, type I, subtype a), oncological, and b) aspecific Endoarteriolar Blocking Devices, which predispose to the related disorders. Finally, only individuals with inherited cerebral biophysical-semeiotic Real Risk may be involved by functional decline, particularly in presence of

Co Q10 deficincy syndrome.

References

1)Stagnaro-Neri M., Stagnaro S., Carenza di Co Q10 secondaria a terapia ipolipidemmizante diagnosticata con la Percussione Ascoltata. Settimana Italiana di Dietologia, 9-13 Aprile 1991, Merano. Atti, pg. 65. Epat. 37, 17, 1990.

2)Stagnaro-Neri M., Stagnaro S., Acidi grassi W-3, scavengers dei radicali liberi e attivatori del ciclo Q della sintesi del Co Q10. Gazz. Med. It. – Arch. Sc. Med. 151, 341, 1992.

3) Stagnaro-Neri M., Stagnaro S., Auscultatory Percussion Coenzyme Q deficiency Syndrome. VI Int. Symp., Biomedical and clinical aspects of Coenzyme Q. Rome, January 22.24, 1990,Chairmen K. Folkers, G.L. Littarru, T. Yamagani, Abs., pg. 105.

4) Stagnaro-Neri M., Stagnaro S., Sindrome clinica percusso-ascoltatoria da carenza di Co Q10. Medic. Geriatr. XXIV, 239.

5) Stagnaro S. Newborn-pathological Endoarteriolar Blocking Devices in Diabetic and Dislipidaemic Constitution and Diabetes Primary Prevention. The Lancet. March 06 2007. http://www.thelancet.com/journals/lancet/article/PIIS0140673607603316/comments?totalcomments=1

6) Stagnaro S. Bedside diagnosis of osteoporotic constitution, real risk of inheriting ostoporosis, and finally osteoporosis. Theoretical Biology and Medical Modelling 21 June 2007. http://www.tbiomed.com/content/4/1/23/comments#285569

7) Stagnaro S. New bedside way in reducing mortality in diabetic men and women. Ann. Int. Med. http://www.annals.org/cgi/eletters/0000605-200708070-00167v1

Biophysical-Semeiotic Consitutions play a pivotal role also in age-related diseases.

Sergio Stagnaro — 2007-06-12T16:22:50Z

Sirs,

we must agree with the statement that biophysical-semeiotic consitutions are as important in all other life-periods as in ageing (1-7). For instance, “Inflammation is not per se a negative phenomenon: it is the response of the immune system to the invasion of viruses or bacteria and other pathogens”. But, not all aged individuals have identical immune system, we can nowadays evaluate at the bedside in precise, rapid, and relaible way (1, 2). In addition, without Oncological Terrain and Oncological Real Risk, localized since birth in a well-defined biological system, oncogenesis is not possible (3-6, 8). Furthermore, aged subjects my be involved by so-called “senile” type 2 diabetes if they are positive SINCE BIRTH for both diabetic “and” dislipidaemic biophysical-Semeiotic Constitutions (7). Interestingly, I demonstrated earlier that all aged persons over 90 years, I meet in my practice during 44 years, were negative for Co Q10 deficiency syndrome (10-12).

1) Stagnaro S., Stagnaro-Neri M., Le Costituzioni Semeiotico-Biofisiche.Strumento clinico fondamentale per la prevenzione primaria e la definizione della Single Patient Based Medicine. Ed. Travel Factory, Roma, 2004. http://www.travelfactory.it

2) Stagnaro S., Stagnaro-Neri M. Single Patient Based Medicine.La Medicina Basata sul Singolo Paziente: Nuove Indicazioni della Melatonina. Ed. Travel Factory, Roma, 2005

3) Stagnaro S., Stagnaro-Neri M., Oncological Terrain, conditio sine qua non of Oncogenesis, 2004: http://www.gutjnl.com/cgi/eletters?lookup=by_date&days=60

4) Stagnaro SergioBiophysical Semeiotic Constitutions, Genomics, and Cardio-Vascular Diseases. BMC Cardiovascular Disorders http://www.biomedcentral.com/1471-2261/4/20/comments#95454

5) Stagnaro Sergio. "Genes, Oncological Terrain, and Breast Cancer" World Journal of Surgical Oncology., 2005, http://www.wjso.com/content/3/1/45/comments#205475

6) Stagnaro Sergio. Single Patient Based Medicine: its paramount role in Future Medicine. Public Library of Science. 2005. http://medicine.plosjournals.org/perlserv/?request=read-response

7) Stagnaro S. Newborne-pathological Endoarteriolar Blocking Devices in Diabetic and Dislipidaemic Constitution and Diabetes Primary Prevention. The Lancet. March 06 2007. http://www.thelancet.com/journals/lancet/article/PIIS0140673607603316/comments?totalcomments=1

8) Stagnaro-Neri M., Stagnaro S. Introduzione alla Semeiotica Biofisica. Il Terreno Oncologico. Ed. Travel Factory, Roma, 2004.

9) Stagnaro S., Stagnaro-Neri M., La Melatonina nella Terapia del Terreno Oncologico e del “Reale Rischio” Oncologico. Ed. Travel Factory, Roma, 2004.

10) Stagnaro S., Ipercolesterolemia e Coenzima Q10. The Pract. Ed. It. 133, 5-6, 1990

11) Stagnaro-Neri M., Stagnaro S., Carenza di Co Q10 secondaria a terapia ipolipidemizante diagnosticata con la Percussione Ascoltata. Settimana Italiana di Dietologia, 9-13 Aprile 1991, Merano. Atti, pg. 65. Epat. 37, 17, 1990

12) Stagnaro-Neri M., Stagnaro S., Sindrome clinica percusso-ascoltatoria da carenza di Co Q10. Medic. Geriatr. XXIV, 239.

Assessing NK cell compartment in individuals with CAD Inherited Real Risk

Sergio Stagnaro — 2007-05-14T10:30:51Z

Sirs,

to certain extent, I agree with the authors of this intriguing article on the importance of studying NK compartment in CAD patients. However, I add someting more: A) we must know that it really exsist the untill now overloked CAD Inherited Real Risk, recognized bedside since birth with a sthetoscope (www.semeioticabiofisica.it). It's characterized by "coronary microcirculatory remodelling", based on altered compliance of coronary arterioles, according to Hammersen, and particularly on newborn-pathological, type I, subtype b), Endoarteriolar Blocking Devices, I discovered (1-3); B)we have to utilize in CAD Primary Prevention the study of NK compartment also in CAD primary prevention, at the condition that we recognize "clinically" those who are at coronary Real Risk, conditio sine qua non of selecting individuals to be enrolled in our research; C) All CAD risk factors (300 or more!) may provoke coronary heart disorder, but exclusively in subjects with Inherited Coronary Real Risk,and evidently not in all. In fact, there are diabetic and/or dyslipidaemic and/or hypertensive, a.s.o., patients,who live as far as advanced age, showing normal coronary vessells! In conclusion, since now all physicians around the world must familiarize with such as new concept in Medicine, i.e., CAD Inherited Real Risk, I'll illustrate in my Lecture at V Virtual International Congress of Cardiology (1st Sept.- 1st Nov., 2007 - organized by FAC, President Prof. Jorge Sanagua - aiming to realize an efficacious CAD Primary Prevention, failing nowadays on the base of expensive present CAD Guide Line.

1)Stagnaro S. Newborn-pathological Endoarteriolar Blocking Devices in Diabetic and Dislipidaemic Constitution and Diabetes Primary Prevention. The Lancet. March 06 2007. http://www.thelancet.com/journals/lancet/article/

PIIS0140673607603316/comments?totalcomments=1

2) Stagnaro S. Rimodellamento Microvascolare, Costituzioni Semeiotico-Biofisiche e Reale Rischio Semeiotico-Biofisico. Ruolo dei Dispositivi Endoarteriolari di Blocco neoformati-patologici, clicmedicina.it, 10/4/2007, http://www.clicmedicina.it/pagine%20n%2028/

rimodellamento.htm

3)Stagnaro S. Biophysical-Semeiotic Diabetic “and” Dyslipidaemic Constitutions and Primary Prevention. Annals of Family Medicine

http://www.annfammed.org/cgi/eletters/4/5/427

We have a lot to learn about 'diseases of the aging'

Trevor Marshall — 2006-12-19T08:22:44Z

In 2004 we described how the chronic inflammatory disease, sarcoidosis, is caused by a life-long accumulation of intra-phagocytic bacterial pathogens[1]. We recently published an update[2], reporting that many chronic inflammatory diseases result from a similar pathogenesis. Our Phase 2 clinical trial has already been demonstrating recovery from some of the diseases of aging, particularly arthritis, osteopenia, and even diabetes[3].

Interestingly, those patients who have recovered from terminal inflammatory conditions, such as sarcoidosis and rheumatoid arthritis, report that recovery feels like "being 20 years younger." We are also observing that the body has an amazing ability to regenerate after inflammatory damage which is currently considered to be 'permanent' (eg, fibrosis and peripheral neuropathy). Clearly we still have a lot to learn about the processes which society categorizes as 'aging'.

Our research points towards Th1 inflammation, the innate immune response to intraphagocytic pathogens, as being the cause of so many "disease of the aging," ranging from atherosclerosis, cardiomyopathy and arthritis through to many neurological conditions, and even to dementia.

We have shown much chronic inflammation results from the body's innate immune response, and we agree it seems likely that 'Inflammaging' may also result from this same pathogenesis.

References:

1. Marshall TG, Marshall FE: Sarcoidosis succumbs to antibiotics - implications for autoimmune disease. Autoimmunity Reviews,2004; 3(4):295-3001

2. Marshall TG: VDR Nuclear Receptor Competence is the Key to Recovery from Chronic Inflammatory and Autoimmune Disease. Abstract presentation, Days of molecular medicine, 2006.

Copy available from URL http://autoimmunityresearch.org/karolinska-handout.pdf

3. Waterhouse JC, Marshall TG, Fenter B, Mangin M, Blaney G: High levels of active 1,25-dihydroxyvitamin D despite low levels of the 25-hydroxyvitamin D precursor - Implications of dysregulated vitamin D for disgnosis and treatment of Chronic Disease. In Vitamin D: New Research. Volume 1. Edited by: Stoltz VD. New York: Nova Science Publishers; 2006. ISBN: 1-60021-000-7

4. Marshall TG: Are statins analogs of vitamin D?. Correspondence to Grimes, DS. The Lancet 2006; 368:1234 doi:10.1016/S0140-6736(06)69509-3

Copy available from URL http://www.thelancet.com/journals/lancet/article/PIIS0140673606695093/fulltext

5. Marshall TG: A New Approach to Treating Intraphagocytic CWD Bacterial Pathogens in Sarcoidosis, CFS, Lyme and other Inflammatory Diseases. American Academy of Environmental Medicine; 2006, Plenary Sessions Syllabus, 41st Annual Meeting.

Copy available from URL http://autoimmunityresearch.org/aaem_2006.ram

6. Marshall TG: Molecular genomics offers new insight into the exact mechanism of action of common drugs - ARBs, Statins, and Corticosteroids. FDA CDER Visiting Professor presentation, FDA Biosciences Library, Accession QH447.M27 2006

Copy available from URL http://autoimmunityresearch.org/fda-visiting-professor-7mar06.ram

7. Marshall TG, Lee RE, Marshall FE: Common angiotensin receptor blockers may directly modulate the immune system via VDR, PPAR and CCR2b. Theor Biol Med Model. 2006 Jan 10;3(1):1. Available from URL http://www.tbiomed.com/content/3/1/1

8.Marshall TG, Fenter BJ, Marshall FE: Antibacterial Therapy Induces Remission in Sarcoidosis (in English). JOIMR 2005;3(1):2 Available from URL http://www.joimr.org/phorum/read.php?f=2&i=107&t=107

Immunoceutic effect of medicinal mushroom extracts

Tang Ch'ang — 2006-05-15T20:05:00Z

I am approaching 80 years of age, living with manageable chronic ailments - Diabetes type 2, high blood pressure, gout but all under control by medication. I am also taking supplements such as Vitamins, Grape Seed Extract and walking exercise to maintain fitness. My life style is quite acceptable. Would I also benefit if I took immune-boosting mushroom extracts as an aid to my weakening immnue system?

Study the immune system in ageing and disease

Gerard Ligthart — 2006-01-21T14:07:18Z

Yes dear colleagues! A warm applause for your article. That is exactly what I was trying to say in my contribution to the discussion in MAD in 2001 (Mech. Ageing Development 2001; 122, 136-140).

Now we are making progress in our concepts of the role of the immune system in ageing.

We, the scientific community interested in Immunology & aging, should help you forward.

I work as a geriatrician in 'pure' practice.

We have access to large numbers of geriatric patients of all levels of frailty. If that could be of any use, let me know, we might also be able to get some funding for a good reseach project.

But in any case: I am very happy with your article as it helps us forward and it stimulates further thinking!

With kind regards,

Prof.dr. Gerard Ligthart, MD, PhD, geriatrician

Department of Geriatric Medicine

Amphia Hospital, Breda, Netherlands

Postal address:

Rynsburgerweg 75

2334 BH Leiden

Netherlands