DSpace Colección :
https://repositorio.uca.edu.ar/handle/123456789/1381
2024-03-29T01:38:55ZA phase II study of the pineal hormones melatonin and 5-methoxytryptamine plus cannabidiol in association with angiotensin 1-7 in the treatment of advanced solid tumour patients eligible for the only best supportive care
https://repositorio.uca.edu.ar/handle/123456789/13686
Título : A phase II study of the pineal hormones melatonin and 5-methoxytryptamine plus cannabidiol in association with angiotensin 1-7 in the treatment of advanced solid tumour patients eligible for the only best supportive care
Autor : Lissoni, Paolo; Porro, Giorgio; Messina, Giusy; Galli, Carla; Di Fede, Giuseppe; Valentini, Agnese; Simoes-e-Silva, Ana Cristina; Cardinali, Daniel Pedro
Resumen : Abstract: The recent advances in the investigation of tumour biology have demonstrated that the human body may produce several
molecules provided by a natural anticancer activity without any toxicity, in particular the pineal hormones melatonin (MLT),
5-methoxytryptamine (5-MTT) and pinealine, the endogenous cannabinoids, oxytocin, and angiotensin 1-7 (Ang 1-7). Unfortunately,
despite their well confirmed anticancer and non-toxic properties, very few clinical studies have been performed in an attempt to
evaluate the potential therapeutic efficacy of the endogenous human anticancer molecules in the treatment of cancer patients, at
least of those eligible for the only palliative therapy. Moreover, most studies have been generally limited to the use of the only pineal
MLT. The present preliminary study was carried out to evaluate the anticancer efficacy of an oral administration of MLT (100 mg in
the dark period) in association with 5-MTT (10 mg in the light period), the cannabinoid agent cannabidiol (CBD) ( 10 mg twice/day)
and Ang 1-7 (0.5 mg/twice day) in a group of 14 untreatable advanced or metastatic cancer patients. The clinical response consisted
of partial response (PR) in 2/14 (14%), and stable disease (SD) in 8/14 (57%). Then, a disease control (PR + SD) was achieved
in 10/14 (71%), whereas the remaining 4/14 (29%) had a progressive disease. Moreover, disease control was associated with a
significant increase in lymphocyte-to-monocyte ratio (LMR), by showing that the control of the neoplastic growth is mediated at
least in part by an improvement in the antitumor immune status of cancer patients.The treatment was well tolerated in all patients,
and in particular no important decline in blood pressure values occurred. On the contrary, a clear improvement in asthenia was
obtained in 8/10 (80%) patients with important asthenia prior to study. This preliminary study may suggest that after the failure
of the common standard anticancer therapies, the administration of the main endogenous anticancer neuroendocrine molecules,
firstly MLT and Ang 1-7, could constitute an alternative approach to cancer patients instead of the simple best supportive care alone.2021-01-01T00:00:00ZA preliminary study of low-dose angiotensin 1-7 plus the pineal hormone melatonin in the treatment of human systemic diseases other than cancer and autoimmune pathologies
https://repositorio.uca.edu.ar/handle/123456789/13684
Título : A preliminary study of low-dose angiotensin 1-7 plus the pineal hormone melatonin in the treatment of human systemic diseases other than cancer and autoimmune pathologies
Autor : Lissoni, Paolo; Porta, Enrica; Rovelli, Franco; Messina, Giusy; Lissoni, Arianna; Porro, Giorgio; Porro, Davide; Di Fede, Giuseppe; Monzon, Alejandra; Sassola, Andrea; Cardinali, Daniel Pedro
Resumen : Abstract: The recent advances of the psychoneuroimmunology have demonstrated the existence of a physiological
anti-inflammatory antitumor neuroendocrine axis, mainly constituted by the pineal gland through its indole
hormone melatonin (MLT) and the ACE2-angiotensin 1-7 (Ang 1-7) system. Moreover, most human systemic
diseases, including cancer, autoimmunity, metabolic, cardiovascular, and neurodegenerative pathologies, have
appeared to be characterized by an endogenous deficiency in the functionless of the pineal gland and ACEACE2 system. Therefore, the exogenous correction of MLT and Ang 1-7 deficiency could improve the clinical
control of human systemic diseases. On these bases, a preliminary study of MLT plus Ang 1-7 was planned
in patients suffering from systemic alterations other than cancer and autoimmunity. The study included 33
consecutive patients, whose pathologies were, as follows: cardiovascular pathologies: 9; pulmonary diseases:
7; metabolic syndrome: 7; neurodegenerative pathologies: 10. Both Ang 1-7 and MLT were given orally, at
a dose of 0.5 mg/day in the morning for Ang 1-7, and at a dose of 10 mg/day in the evening for MLT. The
treatment was well tolerated in all patients, and no-therapy related toxicity occurred. On the contrary, most
patients experienced a relief of anxiety and asthenia, and an improvement in both mood and quality of sleep.
Moreover, most patients referred an increased diuresis. Blood pressure values progressively became within the
normal range in hypertensive patients. On the same way, glucose and cholesterol levels progressively decrease
on therapy in diabetic and hypercholesterolemic patients, respectively. Patients with pulmonary disturbance
referred an important enhancement in the expectoration, with a following improvement in the respiratory
symptomatology. Finally, an apparent improvement in cognitive and motor functions was achieved in patients
with neurodegenerative pathologies. These preliminary results would suggest a future medical possibility to
treat the human systemicdiseases by simply correcting their endogenous neuroendocrine deficiencies, mainly
those involving the functions of the pineal gland and ACE2-Ang1-7 system.2021-01-01T00:00:00ZMelatonin as an add-on treatment of COVID-19 infection : current status
https://repositorio.uca.edu.ar/handle/123456789/13682
Título : Melatonin as an add-on treatment of COVID-19 infection : current status
Autor : Brown, Gregory M.; Pandi Perumal, Seithikurippu R.; Pupko, Harold; Kennedy, James L.; Cardinali, Daniel Pedro
Resumen : Abstract: This brief review was written to provide a perspective on the flurry of reports suggesting
that melatonin can be an important add-on therapy for COVID-19. Despite the passage of more
than 60 years since its discovery and much evidence representing the contrary, there has been great
reluctance to conceive melatonin as anything other than a hormone. Many other body chemicals are
known to have multiple roles. Melatonin was first shown to be a hormone derived from the pineal
gland, to be actively synthesized there only at night, and to act on targets directly or via the G-proteincoupled receptors (GPCRs) superfamily. It is of note that over 40 years ago, it was also established
that melatonin is present, synthesized locally, and acts within the gastrointestinal tract. A wider
distribution was then found, including the retina and multiple body tissues. In addition, melatonin
is now known to have non-hormonal actions, acting as a free radical scavenger, an antioxidant,
and as modulating immunity, dampening down innate tissue responses to invaders while boosting
the production of antibodies against them. These actions make it a potentially excellent weapon
against infection by the SARS-CoV-2 virus. Early published results support that thesis. Recently, a
randomized controlled study reported that low doses of melatonin significantly improved symptoms
in hospitalized COVID-19 patients, leading to more rapid discharge with no side effects, while
significantly decreasing levels of CRP, proinflammatory cytokines, and modulating dysregulated
genes governing cellular and humoral immunity. It is now critical that these trials be repeated, with
dose-response studies conducted and safety proven. Numerous randomized controlled trials are
ongoing, which should complete those objectives while also allowing for a more thorough evaluation
of the mechanisms of action and possible applications to other severe diseases.2021-01-01T00:00:00ZMelatonin : highlighting its use as a potential treatment for SARS‑CoV‑2 infection
https://repositorio.uca.edu.ar/handle/123456789/13681
Título : Melatonin : highlighting its use as a potential treatment for SARS‑CoV‑2 infection
Autor : Reiter, R.; Sharma, Ramaswamy; Simko, Fedor; Domínguez Rodriguez, Alberto; Tesarik, Jan; Neel, Richard L.; Slominski, Andrzej T.; Kleszczynsk, Konrad; Martin‑Gimenez, Verna M.; Manucha, Walter; Cardinali, Daniel Pedro
Resumen : Abstract: Numerous pharmaceutical drugs have been repurposed for use as treatments for COVID-19 disease. These drugs have not
consistently demonstrated high efcacy in preventing or treating this serious condition and all have side efects to difering
degrees. We encourage the continued consideration of the use of the antioxidant and anti-infammatory agent, melatonin, as a
countermeasure to a SARS-CoV-2 infection. More than 140 scientifc publications have identifed melatonin as a likely useful
agent to treat this disease. Moreover, the publications cited provide the rationale for the use of melatonin as a prophylactic
agent against this condition. Melatonin has pan-antiviral efects and it diminishes the severity of viral infections and reduces
the death of animals infected with numerous diferent viruses, including three diferent coronaviruses. Network analyses,
which compared drugs used to treat SARS-CoV-2 in humans, also predicted that melatonin would be the most efective
agent for preventing/treating COVID-19. Finally, when seriously infected COVID-19 patients were treated with melatonin,
either alone or in combination with other medications, these treatments reduced the severity of infection, lowered the death
rate, and shortened the duration of hospitalization. Melatonin’s ability to arrest SARS-CoV-2 infections may reduce health
care exhaustion by limiting the need for hospitalization. Importantly, melatonin has a high safety profle over a wide range
of doses and lacks signifcant toxicity. Some molecular processes by which melatonin resists a SARS-CoV-2 infection are
summarized. The authors believe that all available, potentially benefcial drugs, including melatonin, that lack toxicity should
be used in pandemics such as that caused by SARS-CoV-2.2022-01-01T00:00:00Z