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Recent Patents on Endocrine Metabolic
& Immune Drug Discovery
ISSN: 1872-2148
Recent Patents on Endocrine,
Metabolic & Immune Drug Discovery
Volume 3, Number 1, January 2009
Contents
Recent Patents on the Treatment of Type 1 Diabetes Pp.1-10
Alessandra Fierabracci
[Abstract] [Full
text article]
Plasticity of Neuroendocrine-Immune Interactions
during Ontogeny: Role of Perinatal Programming in Pathogenesis
of Inflammation and Stress-Related Diseases in Adults
Pp. 11-27
Liudmila A. Zakharova
[Abstract] [Full
text article]
Recent Advances on Detection of Modified Forms of
Low-Density Lipoproteins Pp. 28-34
Tanize E. S. Faulin, Maria C. C. Garcia, Dulcineia S.
P. Abdalla
[Abstract] [Full
text article]
Physiology of Immune System: Regulation of Stem Cell
Survival Pp. 35-41
Claudio Arra, Maria C. Turco, Morena D’avenia, Gaetano
Torino, Aldo Giudice and Maria Pascale
[Abstract] [Full
text article]
Current Pharmacological Approaches to Prevent and
Treat Post Menopausal Osteoporosis Pp. 42-53
Rong S. Yang and Shing H. Liu
[Abstract] [Full
text article]
A Proposal for a New Classification of Type 1 Diabetes Mellitus
Based on Clinical and Immunological Evidence Pp.
54-59
Masahito Katahira
[Abstract] [Full
text article]
The Therapeutic Potential of Melatonin in Neurological
Disorders Pp. 60-64
Bhavini Bhavsar, Muhammad U. Farooq and Archit Bhatt
[Abstract] [Full
text article]
Menstrual Cycle and Glycemic Control Pp.
65-68
Ana C. R. Ramalho, Carolina M. Andrade and Fernanda V.
D. O. Prates
[Abstract] [Full
text article]
Current Opinion in the Pharmaceutical Management of
Irritable and Inflammatory Bowel Diseases: Role of ATP
Pp. 69-75
Pooneh Salari and Mohammad Abdollahi
[Abstract] [Full
text article]
Patent Selections Pp. 76-79
[Full
text article]
Abstracts
[Back to top]
Recent Patents on the Treatment of Type 1 Diabetes
Alessandra Fierabracci
[Full
text article]
The incidence of endocrine autoimmunity is increasing
worldwide. Complex molecular and cellular mechanisms underline
the pathogenesis of autoimmune diseases with the contribution
of putative environmental factors and the requisite allele(s)
responsible for antigen presentation by antigen-presenting
cells for T cell recognition. Although genetic factors have
been well dissected, the environmental agents, including putative
viruses, which may be causative of disease, are still under
investigation. The long preclinical period of autoimmune disorders
is characterised by an enhanced challenge over time of autoreactive
T cells by an increased number of autoantigenic peptides and
autoantibodies production. It is of considerable importance
to establish predictive, preventive strategies of the disease
onset. It is also relevant to project novel immunotherapeutic
interventions aiming to halt the disease progression before
and after the clinical manifestations become evident. In this
article, we review the most recent and important patents related
to autoimmune endocrine disorders with special reference to
insulin-dependent diabetes mellitus, Addison’s disease,
Graves’ disease and Hashimoto’s thyroiditis. Engineered
bioactive compounds aim to interfere with T cell activation
and differentiation, to modulate other inflammatory effectors
cells and cytokine production. We discuss the importance of
the novel therapeutic targets in treating the immunopathological
process in these categories of disorders.
[Back to top]
Plasticity of Neuroendocrine-Immune Interactions
during Ontogeny: Role of Perinatal Programming in Pathogenesis
of Inflammation and Stress-Related Diseases in Adults
Liudmila A. Zakharova
[Full
text article]
Experimental and clinical data provide evidence for the lifelong
reciprocal influence of mammalian neuroendocrine and immune
systems. The functions of these systems change during ontogeny.
In the perinatal period, the neuroendocrine system has both
regulatory and morphogenetic functions: during early ontogeny,
neurohormones stimulate the growth and differentiation of
fetal tissues, including the lymphoid tissue. In postnatal
life, effects of many hormones on the immune system are apparently
unspecific: their function is mainly to maintain its homeostasis
in the changing environment. Thymic peptides regulate the
production of hormones, neuropeptides, and cytokines both
in the thymus and in the hypothalamus, pituitary, and gonads.
The perinatal period is critical for the complete structural
and functional development of these systems. Disturbances
in neuroendocrine-immune interactions at this stage result
in long-lasting predisposition to various pathologies in adulthood.
The plasticity of physiological systems in the perinatal period
allows the environmental factors acting on the mother and
fetus to alter the functions of certain organs and tissues,
providing for fetal adaptation to adverse conditions. Exposure
to stress, adverse environmental factors, etc., as well as
mother’s improper diet and behavior during pregnancy
and breast feeding put the young at risk for autoimmune, allergic,
metabolic, psychic, and nervous disorders during adult life.
The possibility of using neurohormones for treating immunodeficiencies
caused by various adverse factors is discussed. The review
also includes recent patents relevant to the problem at issue.
[Back to top]
Recent Advances on Detection of Modified Forms of
Low-Density Lipoproteins
Tanize E. S. Faulin, Maria C. C. Garcia, Dulcineia S.
P. Abdalla
[Full
text article]
Modifications in the structure of native LDL that are capable
of inducing aggregation and/or fusion of the particles are
currently recognized to be a prerequisite for the initiation
of lipid accumulation in arterial intima. Modified forms of
LDL can play an important role on atherogenesis and atherosclerosis
progression, inducing atherosclerosis through complex inflammatory
and immunological mechanisms. LDL can be modified by oxidation,
glycation, alkylation and nitration, among other reactions.
All modifications of LDL can generate neoepitopes, which become
LDL immunogenic. Since modified forms of LDL are associated
with several pathological states, monitoring their levels
in human plasma would be very useful for studying atherogenesis.
Monoclonal antibodies are powerful tools in identifying specific
structures on heterogeneously modified LDL particles. Monoclonal
antibodies specific for epitopes on modified lipoproteins
have been obtained and used for developing diagnosis kits
to evaluate the concentrations of modified lipoproteins in
blood plasma and other biological fluids. Most of the tests
concerning to the assay of modified LDL are ELISAs. More recently,
immunosensor systems, based on the biosensor technologies,
begin to be developed. In this review, the recent advances
on the assessment of these modified LDL particles and related
patents will be discussed.
[Back to top]
Physiology of Immune System: Regulation of Stem Cell
Survival
Claudio Arra, Maria C. Turco, Morena D’avenia, Gaetano
Torino, Aldo Giudice and Maria Pascale
[Full
text article]
The immune system is a complex defense mechanism, able to
protect the body against pathogens. It consists of a network
of cells, tissues, and organs that work together to protect
the body. Leukocytes are key operatives of the immune system.
Cells destined to become immune cells, like all blood cells,
arise in your body's bone marrow from stem cells (HSC). A
large body of evidence show the transcription factors play
critical roles in the homeostasis of T cells, B cells, neutrophils
and other non-lymphoid leneages.
This review discusses the role of the Smek (Suppressor of
mek null) gene, that acts in the stress response pathway of
animals by binding to and enhancing the transcription of FoxO
transcription factors. Furthermore, the review deals with
tachykinins, involved in neurotransmission and immune/hematopoietic
modulation. Both molecules, objects of recent patents, may
have real therapeutic potential.
[Back to top]
Current Pharmacological Approaches to Prevent and
Treat Post Menopausal Osteoporosis
Rong S. Yang and Shing H. Liu
[Full
text article]
Osteoporosis characterized by low bone mass and structural
deterioration of bone tissue; has a huge impact on public
health through high morbidity, mortality and economic costs
associated with resultant fractures. The prevention and treatment
of fragility fractures in the osteoporosis patients worldwide
becomes an important issue in the current clinical practice.
Women often have an accelerated bone loss after menopause
and result in a lower bone mass than men. Since the bone loss
is irreversible, early prevention and treatment of osteoporosis
is important in the early postmenopausal period. The goal
of prevention needs to be not only effective, but also safe,
to diminish the risk of vertebral, hip and other nonvertebral
fractures. Non-pharmacological treatments, such as calcium,
vitamin D, exercise and reduction of risk factors may diminish
the impact of menopause and age-mediated bone loss. Current
pharmacological options available include bisphosphonates,
calcitonin, hormone replacement therapy, selective estrogen
receptor modulators, teriparatide, and strontium ranelate,
etc. Lots of natural products including dietary components
and herbal products have also been demonstrated to be capable
of modifying bone metabolism, particularly of inhibiting bone
resorption. These natural products may provide as an alternative
treatment for osteoporosis. More than 150 patents have recently
been issued for the prevention and treatment of postmenopausal
osteoporosis. The development of other new medications also
sheds light on either prevention or treatment of osteoporosis,
such as human monoclonal anti-RANKL antibody, cathepsin K
inhibitors, and cannabinoid-based drugs.
[Back to top]
A Proposal for a New Classification of Type 1 Diabetes Mellitus
Based on Clinical and Immunological Evidence
Masahito Katahira
[Full
text article]
To better understand the pathogenesis of Type 1 diabetes,
we have developed a new classification of Type 1 diabetes
based on islet autoantibodies, mode of disease onset and insulin
deficiency. The first marker is mode of disease onset and
insulin deficiency, i.e. fulminant-onset (F), acute-onset
(A), slow-onset and insulin-deficient (S),
and slow-onset and non-insulin-deficient (N). The
second marker is islet autoantibodies- a) positive
(autoimmune) or b) negative (idiopathic). The combination
of the four uppercase (F, A, S, and N) and
two lowercase (a and b) letters indicates
the clinical type of diabetes. Therefore, Type 1 diabetes
is the sum of Fa, Fb, Aa, Ab, Sa and Na
types of diabetes, while Type 2 diabetes is the sum of Sb
and Nb types of diabetes. For example, fulminant
Type 1 diabetes is the sum of Fa and Fb
types of diabetes. Classic Type 1 diabetes is the sum of Fa
and Aa types of diabetes. Latent autoimmune diabetes
in adults (LADA) is the sum of Sa and Na
types of diabetes, in which disease onset was in adulthood.
An appropriate classification would improve our understanding
of the pathogenesis of Type 1 diabetes and allow for easier
discrimination of Type 1 diabetes from Type 2 diabetes. This
review article also discusses some recent patent related to
the field.
[Back to top]
The Therapeutic Potential of Melatonin in Neurological
Disorders
Bhavini Bhavsar, Muhammad U. Farooq and Archit Bhatt
[Full
text article]
Melatonin (N-acetyl-5- methoxytryptamine) is a pineal gland
hormone, synthesized from amino acid L-tryptophan. Other tissues
including retina, skin, and gastrointestinal tract also synthesize
it. It is secreted into the cerebrospinal fluid and circulatory
system in a circadian pattern. Its production is light:dark
dependent and its levels are low during the day and maximal
during the hours of darkness. It plays an important role in
different physiological and pathophysiological processes in
the brain, which includes regulation of biological rhythms
and seasonal reproduction. Its biological activity is associated
with its action on melatonin receptors - ML-1 and ML-2. It
has antioxidant and neuroprotective propertities and potential
therapeutic role in different neurological disorders. Melatonin
has been used as a sleep-promoting agent; more recently it
has also been used in headache, movement disorders, neuropathic
pain, and seizure disorders. In this review, some recent patents
also discussed.
[Back to top]
Menstrual Cycle and Glycemic Control
Ana C. R. Ramalho, Carolina M. Andrade and Fernanda V.
D. O. Prates
[Full
text article]
Women with type 1 diabetes frequently report problems with
blood glucose control around the time of menstruation. Although
this issue has been extensively studied, the correlation between
the phases of the menstrual cycle and blood glucose control
remains to be established. This present study discusses the
controversy that exists in the current literature regarding
the effect of the menstrual cycle on metabolic control in
women with type 1 diabetes. A search was made in the PubMed
database in March 2008 of papers published in the last fifteen
years that included the terms “menstrual cycle”
and “type 1 diabetes”. Six articles were selected.
In some women with type 1 diabetes, premenstrual hyperglycemia
has been reported as being detrimental to adequate blood glucose
control. Many factors have been attributed to this phenomenon.
Some studies have reported elevated progesterone levels during
premenstrual hyperglycemia. Other studies have suggested that
premenstrual symptoms may explain the unsatisfactory blood
glucose control found during this period. Despite conflicting
reports in the literature, it would appear that premenstrual
hyperglycemia does occur in some diabetic women. More studies
with larger sample sizes and reliable methodology have been
recommended. This review also took into consideration the
registration of some recent patents.
[Back to top]
Current Opinion in the Pharmaceutical Management of
Irritable and Inflammatory Bowel Diseases: Role of ATP
Pooneh Salari and Mohammad Abdollahi
[Full
text article]
Inflammatory bowel disease (IBD) and irritable bowel
syndrome (IBS) are two chronic intestinal diseases having
a mutual pathophysiological pathways with different manifestations.
Generally, inflammatory mediators and cytokines orchestrate
the scenario that amongst them, tumor necrosis factor-alpha
(TNF-α)
is a cornerstone. Nowadays different medications and drug
classes are administered for treatment of IBD and IBS but
there is no full cure and side effects of drugs limit their
usage. Concerning the novel suggestion of ATP in the treatment
of bowel diseases, we were invited to conduct a systematic
review. MeSh keywords of IBD, IBS, TNF-α,
IL-12, and ATP were searched in search engines like Pubmed,
Scopus, Web of sciences, Embase, and Google scholar. Comparing
the common medications with ATP in terms of side effects,
efficacy, and other limitations lead us to the conclusion
that ATP could be a reasonable alternative that may replace
all other medications in this field in the near future. ATP
is prepared as lyophilized form that is stable at room temperature
for at least 1-3 years and can be used as intravenous infusion
in the setting of private homes without direct medical supervision.
Other routes of administration include intraperitoneal, subcutaneous,
oral, topical, nasal, and sublingual. Also, it can be mixed
with parenteral and enteral nutrition cocktails. The review
also discussed some recent patents relevant to the field.
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