Afonso Caricati-neto

Universidade Federal de São Paulo - Escola Paulista de Medicina, Brazil · Pharmacology

Aims: Although reduced life expectancy in Parkinson's Disease (PD) patients has been related to severe cardiac arrhythmias due to autonomic dysfunctions, its molecular mechanisms remain unclear. To investigate the role of cardiac β1-Adrenergic (β1AR) and A1-Adenosine (A1R) receptors in these dysfunctions, the pharmacological effects of stimulation...

Background: Although several studies suggest that heparins prevent arrhythmias caused by acute myocardial infarction (AMI), the molecular mechanisms involved remain unclear. To investigate the involvement of pharmacological modulation of adenosine (ADO) signaling in cardiac cells by a low-molecular weight heparin (enoxaparin; ENOX) used in AMI the...

Loperamide is a synthetic opioid commonly used as an antidiarrheal due to its activation of u-opioid receptors in the myenteric plexus. In therapeutic doses, it inhibits peristalsis and has anti-secretory and anti-motility effects, until metabolized by intestinal and hepatic CYP3A4 and CYP2C8 into inactive metabolites. Furthermore, loperamide also...

Pacientes oncológicos, geralmente, são submetidos a tratamentos quimioterápicos e radioterápicos, os quais tendem a causar problemas relacionados a intensos processos inflamatórios, de desnutrição, náuseas e êmese. Por isso, realizar a suplementação nestes pacientes é importante e necessário, pois isso favorece o paciente oncológico sob o ponto de...

Purpose To evaluate the preventive cardioprotective effects of resveratrol and grape products, such as grape juice and red wine, in animal model of cardiac ischemia and reperfusion. Methods Male Wistar rats orally pretreated for 21-days with resveratrol and grape products were anesthetized and placed on mechanical ventilation to surgically induce...

Abstract: Purpose: To evaluate whether the attenuation of mitochondrial Ca2+ overload produced by pharmacological blockade of mitochondrial Ca2+ uniporter (MCU) protects the myocardium against injuries caused by cardiac ischemia and reperfusion (CIR). Methods: CIR was induced in adult male Wistar rats (300-350 g) by occlusion of the left anterior...

Most severe manifestations of COVID‐19 cases, such as multiple organ failure and death, have been linked to coagulation dysfunction markers, such as platelet reduction and increases in prothrombin time, fibrin degradation products and, mainly, D‐dimer [1]. A recent paper by Tang et al. [2] in this journal reported that heparin treatment reduced mor...

Clinically characterized by motor dysfunctions such as bradykinesia, rigidity, and resting tremor, Parkinson's disease (PD) is considered the second most common neurodegenerative disease in developed countries. Although these dysfunctions result from a degeneration and death of dopamine (DA) neurons in the substantia nigra (SN), PD etiology remains...

Clinically characterized by motor dysfunctions such as bradykinesia, rigidity, and resting tremor, Parkinson's disease (PD) is considered as the second most common neurodegenerative disease in developed countries. Although these dysfunctions result from a degeneration and death of dopamine (DA) neurons in the substantia nigra (SN), the PD etiology...

Ischemic heart diseases (IHD) are the leading cause of death worldwide. Although the principal form of treatment of IHD is myocardial reperfusion, the recovery of coronary blood flow after ischemia can cause severe and fatal cardiac dysfunctions, mainly due to the abrupt entry of oxygen and ionic deregulation in cardiac cells. The ability of these...

Parkinson’s disease (PD) is one of the most common age-related neurodegenerative disorders. Several studies over the last few years have shown that PD is accompanied by high rates of premature death compared with healthy controls. Death in PD patients is usually caused by determinant factors such as pneumonia, and cerebrovascular and cardiovascular...

Purpose: To evaluate the cardioprotective response of the pharmacological modulation of β-adrenergic receptors (β-AR) in animal model of cardiac ischemia and reperfusion (CIR), in spontaneously hypertensive (SHR) and normotensive (NWR) rats. Methods: CIR was induced by the occlusion of left anterior descendent coronary artery (10 min) and reperf...

Ischemic heart diseases (IHD) are the leading cause of death worldwide. Although the principal form of treatment of IHD is myocardial reperfusion, the recovery of coronary blood flow after ischemia can cause severe and fatal cardiac dysfunctions, mainly due to the abrupt entry of oxygen and ionic deregulation in cardiac cells. The ability of these...

This book extends the original concept of the “calcium paradox” discovery, herein compiling more than 300 references in the field of calcium ion (Ca2+/cAMP) signalling pathways, neurotransmission and neurodegeneration, and neurological and psychiatric diseases. In this second edition, novel illustrations and tables (highlighting current medicines f...

Purpose: To investigate the cardioprotective effects of ischemic preconditioning (preIC) and postconditioning (postIC) in animal model of cardiac ischemia/reperfusion. Methods: Adult rats were submitted to protocol of cardiac ischemia/reperfusion (I/R) and randomized into three experimental groups: cardiac I/R (n=33), preCI + cardiac I/R (n=7) a...

Background: Blockage of the Na⁺/Ca²⁺ exchanger (NCX) is used to determine the role of NCX in arrhythmogenesis. Trisulfated heparin disaccharide (TD) and Low Molecular Weight Heparins (LMWHs) can directly interact with the NCX and accelerate its activity. Objective: In this work, we investigated the antiarrhythmic effect of heparin oligosaccharides...

Due to the involvement of the imbalance of neuronal Ca2+ homeostasis in the pathogenesis of several neurodegener-ative diseases, the use of drugs to prevent or attenuate this imbalance emerged as a new therapeutic strategy for treating these diseases. Thus, our discovery of the involvement of the interaction between intracellular signaling pathways...

Purpose: To evaluate in vivo animal model of cardiac ischemia/reperfusion the cardioprotective activity of pancreatic lipase inhibitor of the orlistat. Methods: Adult male Wistar rats were anesthetized, placed on mechanical ventilation and underwent surgery to induce cardiac I/R by obstructing left descending coronary artery followed by reperfus...

Since 70´s, the sympathetic hyperactivity due to increment of catecholamine plasma levels is the main adverse effect reported by hypertensive patients that use L-type Ca 2+ channel blockers (CCBs). Our discovery of the involvement of interaction between the intracellular signalling pathways mediated by Ca 2+ and cAMP (Ca 2+ /cAMP interaction) revea...

Alzheimer's disease (AD) is a debilitating neuropsychiatric disorder characterized by the multifaceted decline in cognitive and behavioral functions. Due to the multifaceted nature of AD pathology and our limited understanding on its etiology, AD is difficult to be treated with currently available pharmaceuticals. Then, new therapeutic strategies f...

About 4 years ago, we showed that the paradoxical effects (sympathetic hyperactivity) induced by L-type voltage-activated Ca 2+ channels (VACC) blockers, named by us "calcium paradox" phenomenon, were potentiated by drugs which increase cytosolic cAMP concentration ([cAMP] c-enhancers), for example rolipram, IBMX and forskolin, indicating that the...

The solution for the so-called "calcium paradox" has been revealed 4 years ago, when we demonstrated the involvement of the interaction between Ca 2+ and cAMP signalling pathways (Ca 2+ /cAMP signalling interaction) in this enigma. The "calcium paradox" emerged 4 decades ago, when numerous clinical studies have concluded that prescription of L-type...

Purpose: To investigate the effects of atenolol in inflammatory mediator and oxidative stress in a myocardial injury by intestinal ischemia/reperfusion in rat model. Methods: Adult Wistar male rats were randomly (n=8), anesthetized and divided in: Sham: submitted to operation only; group SS+IR: intravenous saline infusion following superior mese...

Caricati-Neto A, Bergantin LB. Huntington´s disease and the interaction between Ca 2+ and cAMP signaling pathways. J Pharmacol Res December-2017;1(1):17-24. Huntington disease (HD) is a neurodegenerative disease known by progressive motor, behavioral, and cognitive decline that culminates in the death. HD therapy is yet unsatisfactory. Chorea and p...

It is well recognized that an imbalance of intracellular Ca 2+ homeostasis contributes to the pathogenesis of neurodegenerative diseases, such as Alzheimer's (AD). Therefore, regulation of intracellular Ca 2+ homeostasis may represent a new target for treatment of this disease. Our recent discovery of the participation of the interaction between in...

Cancer is a major public health problem and the second leading cause of mortality around the world. Antitumor immunotherapy using monoclonal antibodies is considered selective and efficient in the treatment of different types of tumors, but its cost and toxic effects limit its application. Many tumor microenvironments, including lymphoma and carcin...

According to a 2015 United Nations report on world population ageing, the number of people aged 60, and older, worldwide can double in the next 35 years, reaching almost 2.1 billion people. The growing increment in the life expectancy of the world's population has increased the concern about the age-related neurodegenerative diseases, such as Alzhe...

The pharmaceutical intervention on the interaction between intracellular signaling pathways mediated by Ca2+ and cAMP (Ca2+/cAMP signaling interaction) could bring important benefits for combating neurodegeneration and diseases related to aging. This discovery emerged from classical neurotransmission studies using rodent vas deferens as a model. Fr...

The technique of fluorescence microscopy has become an essential tool in the biomedical sciences. In all living cells, cellular, physiological, and pathological phenomena are accompanied by ionic changes. Then, the development of this technique that allows the measurement of intracellular ion activities has contributed substantially to understandin...

Background: Acute myocardial infarction (AMI) is characterized by ischemic lesions that severely compromise the cardiac structure/function, besides the survival of mammals. Although conventional therapy uses cardiac reperfusion, this procedure increases the cardiac damage caused by ischemia. Methods: Adult male Wistar rats (NWR) were anesthetized,...

This editorial highlights the relevance of interfering in cancer cell progression through the pharmacological manipulation on the cell metabolism of cyclic nucleotides such as cAMP, and on the intracellular Ca2+ signaling, which may avail the reduction of toxic effects promoted by chemotherapy, radiotherapy and immunotherapy, thus decreasing the in...

To study cardioprotective drugs, we developed a simple and efficient methodology to evaluate effects of drugs on cardiac electrical activity using electrocardiogram (ECG) in rats submitted to cardiac ischemia-reperfusion (I/R). Using adult male Wistar rats (14-16-week-old) anesthetized (urethane 1.25 g/kg, i.p.) and kept under mechanical ventilatio...

Introdução: A hipertensão arterial é um dos fatores de risco para doenças cardiovasculares, estando diretamente associada ao elevado consumo de sódio. Objetivo: Avaliar os níveis de marcadores de lesão hepática, renal e cardíaca em ratos hipertensos comparados aos seus controles normotensos, tratados com um salgante isento de sódio, água ou NaCl. M...

It is well established that an imbalance of intracellular Ca 2+ homeostasis contributes to the disease progression of neurodegenerative illnesses related to aging, such as Alzheimer's disease (AD). Therefore, regulation of intracellular Ca 2+ homeostasis may represent a new strategy for treatment of this disease. Our recent discovery of the involve...

Amyotrophic lateral sclerosis (ALS) is a devastating neurological disease characterised by progressive muscular paralysis reflecting selective degeneration and death of motor neurons in the primary motor cortex, brainstem and spinal cord. Several evidences suggest the involvement of the imbalance of the intracellular Ca2+ homeostasis in the death o...

It has been almost 4 years since we revealed the solution for the enigma of the so-called “calcium paradox”. Our discovery of the involvement of Ca2+/cAMP signaling interaction in the regulation of neurotransmitter release, and neuro protection, was clearly a serendipitous discovery. It has produced new avenues in the understanding of the cellular...

Cell signaling is a crucial event for the survival and progress of normal cellular functions. However, mutations of certain genes can lead to the emerging of cancer cells, which can use these signaling mechanisms for their survival, growth and dissemination. Among these mechanisms, we highlight the role of cyclic nucleotides such as cAMP, and Ca2+...

An emerging word in biomedical research nowadays is the " translational research ". Basically, " translating " current knowledge from basic science to approaches for treating human disease-from bench to bedside-is the main concept. Our discovery entitled " calcium paradox " fits properly in this main concept. The enigma of the " calcium paradox " i...

The interaction between intracellular signalling pathways mediated by Ca2+ and cAMP (Ca2+/cAMP signalling interaction) is now well-accepted as a vital cellular process for mammalians. In the neuroscience field, it has opened a new avenue for the drug development more effective, and safer, for the treatment of Alzheimer´s and neurodegenerative disea...

Clinical research plays an important role in medical sciences by determining the safety and efficiency of medications, devices and diagnostic products for human use. Our discovery of the interactions between intracellular signaling pathways as mediated by Ca 2+ and cAMP (Ca 2+ /cAMP signaling interaction) in neurotransmission could help improve cli...

Cardiovascular diseases (CD) are one of the main causes of death in the world, among them is ischemic cardiac disease (ICD). ICD is believed to cause 26 million deaths worldwide by 2030 [1,2]. Among ICD, acute myocardial infarction (AMI) is the most common cause of morbidity and mortality in the world [2,3]. AMI is characterized by a long period, a...

It is now well-established that the signalling pathways mediated by Ca 2+ and cAMP can interact (Ca 2+ /cAMP signalling interaction), thus playing a vital role in cellular processes of mammalians. In the neurology and medicine, it has opened novel opportunities for the development of pharmaceuticals more efficient, and safer, for treating neurodege...

The pharmacotherapy for treating depression is clearly limited. The classical pharmacotherapy that exists nowadays was developed decades ago. Indeed, depression is characterized by reduction of neurotransmitters release in central nervous system, mainly serotonin and catecholamines. Besides, since 70´s several clinical studies have reported that ad...

This discusses how pharmacological modulation of the Ca2+/cAMP signaling interaction could be an important neuroprotective and cardioprotective strategy to protect the dopaminergic neurons from cell death related to Parkinson’s disease (PD) and at the same time to prevent the cardiac collapse in sudden unexpected death in PD.

Several experimental studies performed since 1975, using smooth muscles richly innervated by sympathetic nerves to exclude the autonomic influence of adjusting reflex (rodent vas deferens), showed that L-type voltage-activated Ca 2+ channels (VACC) blockers completely inhibited neurogenic contractions induced by electrical field stimulation (EFS) i...

In 2013, we showed that the paradoxical effects (sympathetic hyperactivity) induced by L-type voltage-activated Ca2+ channels (VACC) blockers, named by us “calcium paradox” phenomenon, were potentiated by drugs which increase cytosolic cAMP concentration ([cAMP]c-enhancers), for example rolipram, IBMX and forskolin, indicating that the sympathetic...

The sympathetic hyperactivity, and tachycardia, are the main adverse effects reported since 70´s by hyperten-sive patients that use L-type Ca 2+ channel blockers (CCBs). Our discovery revealed that the sympathetic hyperactivity was resulting of increase of transmitter release from sympathetic neurons stimulated by CCBs due to its interference on th...

What have we learned from the discovery of the " calcium paradox " due to Ca 2+ /cAMP interaction? Our discovery of the involvement of interaction between the intracellular signalling pathways mediated by Ca 2+ and cAMP (Ca 2+ /cAMP interaction) in the neuronal protection has produced new paths for the understanding of the cellular and molecular me...

It is now well-accepted that the interaction between intracellular signalling pathways mediated by Ca 2+ and cAMP (Ca 2+ /cAMP signalling interaction) plays as a key role in cellular processes of mammalians. In the clinical pathology field, it has opened a new avenue for the drug development more effective, and safer, for the treatment of neurodege...

This editorial focus on the new therapeutic perspectives for Alzheimer's and Parkinson's diseases based on the pharmacological modulation of the Ca2+/cAMP signaling interaction.

It is well recognized that an imbalance of intracellular Ca2+ homeostasis contributes to the pathogenesis of neurodegenerative diseases, such as Alzheimer's (AD). Therefore, regulation of intracellular Ca2+ homeostasis may represent a new target for treatment of this disease. Our recent discovery of the participation of the interaction between intr...

This editorial article gives insights for the inhibition of cancer progression. The pharmacological modulation of Ca2+/cAMP signalling interaction is also cited.

It has been almost 4 years since we revealed the explanation for the enigma of the so-called " calcium paradox ". Interestingly, this discovery initiated decades ago when numerous clinical studies have reported that use of L-type Ca 2+ channel blockers (CCBs) by hypertensive patients decreased arterial pressure, but produced typical symptoms of sym...

Editorial: Without a doubt, we decided to initiate our first editorial article in this journal with the transcription of the " prologue " of our book: From discovering " calcium paradox " to Ca2+/cAMP interaction: Impact in human health and disease...

Our discovery of the involvement of the interaction between intracellular signalling pathways mediated by Ca2+ and cAMP (Ca 2+ /cAMP interaction) in the neurotransmission and neuroprotection has produced new avenues in the understanding of the cellular and molecular mechanisms involved in the pathogenesis of neurological and psychiatric disorders,...

It has been almost 4 years since we revealed the explanation for the enigma of the so-called " calcium paradox ". Our discovery of the involvement of Ca 2+ /cAMP signaling interaction in the regulation of neurotransmitter release, and neuroprotection, was clearly a serendipitous discovery. It has produced new avenues in the understanding of the cel...

Depression is a psychiatric disease resulting mainly by dysfunction of serotoninergic and monoaminergic neurotransmission in central nervous system (CNS). Due to the multifaceted nature of depression and our limited understanding on its etiology, depression is difficult to be treated with currently available pharmaceuticals. Then, new therapeutic s...

In the cardiovascular field, tachycardia and increment of catecholamine plasma levels (sympathetic hyperactivity) have been reported by hypertensive patients that use L-type Ca2+ channel blockers (CCBs) since 70´s. Our discovery of the involvement of interaction between the intracellular signalling pathways mediated by Ca2+ and cAMP (Ca2+/cAMP inte...

Our discovery entitled " calcium paradox " phenomenon due to interaction of intracellular signalling pathways mediated by Ca 2+ and cAMP (Ca2+/cAMP interaction) may provide new avenues for the treatment of neurologi-cal disorders, such as Alzheimer´s disease. This disease is resulting by reduction of acetylcholine release in central nervous system...

Abstract It is well established that an imbalance of neuronal Ca2+ homeostasis contributes to the pathogenesis of neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's (PD) diseases. Therefore, regulation of neuronal Ca2+ homeostasis may represent a new therapeutic strategy of these diseases. Our recent discovery of the involvement o...

The pharmacological manipulation of interaction of the intracellular signalling pathways mediated by Ca 2+ and cAMP (Ca 2+ /cAMP interaction) may provide new insights for the pharmacotherapy of psychiatric disorders, dramatically impacting clinical pharmacology and translational medicine. Disorders mainly resulting by reduction of serotonin and cat...

Our discovery of the involvement of the interaction between intracellular signalling pathways mediated by Ca2+ and cAMP (Ca2+/cAMP signaling interaction) in the neurotransmission and neuroprotection has produced important advances in the understanding of the pathophysiology and pharmacology of neurological and psychiatric disorders, such as Alzheim...