Sérgio Henrique Ferreira (October 4, 1934 – July 17, 2016) was a Brazilian physician and

pharmacologist Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemic ...

noted for the discovery of the bradykinin potentiating factor, which led to new and widely used anti- hypertension drugs — the

ACE inhibitors Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of high blood pressure and heart failure. They work by causing relaxation of blood vessels as well as a decrease in blood volum ...

Biography

Ferreira received his

M.D. Doctor of Medicine (abbreviated M.D., from the Latin ''Medicinae Doctor'') is a medical degree, the meaning of which varies between different jurisdictions. In the United States, and some other countries, the M.D. denotes a professional degree. T ...

from the Faculty of Medicine of Ribeirão Preto of the University of São Paulo (USP) and soon became staff member of the same school, where he was a member of the Department of

Pharmacology Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemi ...

. His research training in pharmacology initiated in this Department with Prof. Maurício Rocha e Silva, the discoverer of

bradykinin Bradykinin (BK) (Greek brady-, slow; -kinin, kīn(eîn) to move) is a peptide that promotes inflammation. It causes arterioles to dilate (enlarge) via the release of prostacyclin, nitric oxide, and endothelium-derived hyperpolarizing factor and m ...

. While working on this subject, he discovered a family of

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. ...

s present in the venom of a Brazilian snake, ''

Bothrops jararaca ''Bothrops jararaca'' — known as the ''jararaca'' or ''yarara'' — is a highly venomous pit viper species endemic to South America in southern Brazil, Paraguay, and northern Argentina. The specific name, ''jararaca'', is derived from the Tupi ...

'', which inhibited kininase activity and strongly potentiated the effects of bradykinin ''in vivo'' and ''in vitro''. This factor was named bradykinin potentiating factor, BPF. In 1968, with the collaboration of Dr. Lewis Joel Greene, from the

Brookhaven National Laboratory Brookhaven National Laboratory (BNL) is a United States Department of Energy national laboratory located in Upton, Long Island, and was formally established in 1947 at the site of Camp Upton, a former U.S. Army base and Japanese internment c ...

, U.S., he isolated several pharmacologically active peptides responsible for the activity of BPF. Using those peptides, was demonstrated a general parallelism between bradykinin potentiation and inhibition of

Angiotensin Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adr ...

I conversion. Subsequently, his group elucidated the structure of the smallest peptide, and using the synthetic pentapeptide, demonstrated its ability to potentiate bradykinin and to inhibit the conversion of angiotensin I in vivo in experimental models of hypertension. His work in this area paved the way for the development of a new class of antihypertensive drugs, the angiotensin converting enzyme (ACE) inhibitors by

Squibb Squib or Squibb may refer to: * Squib (explosive), a miniature explosive with a very small charge ** Bullet hit squib, a practical effect simulating a gunshot wound in film and theatre * Squib (''Harry Potter'') * Squib (''Star Wars'') * Squib ( ...

scientists. For this work with the Bothrops peptide he received the CIBA Award for Hypertension Research of 1983, together with Drs. E. Ondetti and D. Cushman from Squibb laboratories. While working in

London London is the capital and List of urban areas in the United Kingdom, largest city of England and the United Kingdom, with a population of just under 9 million. It stands on the River Thames in south-east England at the head of a estuary dow ...

in the early 1970s with

John R. Vane Sir John Robert Vane (29 March 1927 – 19 November 2004) was a British people, British pharmacologist who was instrumental in the understanding of how aspirin produces pain-relief and anti-inflammatory effects and his work led to new treatments ...

(

Nobel prize The Nobel Prizes ( ; sv, Nobelpriset ; no, Nobelprisen ) are five separate prizes that, according to Alfred Nobel's will of 1895, are awarded to "those who, during the preceding year, have conferred the greatest benefit to humankind." Alfre ...

in Medicine, 1983), he participated in the discovery of the inhibition of the synthesis of

prostaglandins The prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are deri ...

aspirin Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat in ...

-like drugs. At that time, he proposed that the mechanism of the

analgesic An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...

action of

nonsteroidal anti-inflammatory drug Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...

s (NSAIDs) was due to the prevention of

pain receptor A nociceptor ("pain receptor" from Latin ''nocere'' 'to harm or hurt') is a sensory neuron that responds to damaging or potentially damaging stimuli by sending "possible threat" signals to the spinal cord and the brain. The brain creates the sens ...

sensitization Sensitization is a non-associative learning process in which repeated administration of a stimulus results in the progressive amplification of a response. Sensitization often is characterized by an enhancement of response to a whole class of st ...

which results from an inhibition of the synthesis of prostaglandins. This hypothesis was supported by further work from his laboratory and from many other investigators. His studies on the basic mechanisms involved in the development of inflammatory

hyperalgesia Hyperalgesia ( or ; 'hyper' from Greek ὑπέρ (huper, “over”), '-algesia' from Greek algos, ἄλγος (pain)) is an abnormally increased sensitivity to pain, which may be caused by damage to nociceptors or peripheral nerves and ca ...

led to the discovery that a select class of analgesics like

metamizole Metamizole, or dipyrone, is a painkiller, spasm reliever, and fever reliever that also has anti-inflammatory effects. It is most commonly given by mouth or by intravenous infusion. Although it is available over-the-counter in some countries ...

, in contrast to the classical NSAIDs, are able to counteract the ongoing sensitization of the primary sensory neuron via the stimulation of the

arginine Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) and both the a ...

nitric oxide Nitric oxide (nitrogen oxide or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes denoted by a dot in its ...

pathway. He characterized a phenomenon described as retrograde sensitization of the primary sensory neuron, which emphasizes the importance of the peripheral component of the inflammatory pain. His group made a relevant contribution to the role of bradykinin and of

cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in a ...

s in the development of inflammatory hyperalgesia. He found that among the cytokines,

interleukin Interleukins (ILs) are a group of cytokines (secreted proteins and signal molecules) that are expressed and secreted by white blood cells (leukocytes) as well as some other body cells. The human genome encodes more than 50 interleukins and rela ...

1b mediates the endogenous release of prostaglandins and IL-8 is responsible for the development of the sympathetic hyperalgesia. In this area he described an antagonist of IL-1 that is now being developed as a model for a new class of analgesics.

Awards and accolades

Ferreira's contributions to science are extensively recognized. In 1995, He received the National Order of Scientific Merit in the Great Cross level, and received several awards and medals, such as the

TWAS Prize This is a list of recipients of the TWAS Prize, awarded annually by The World Academy of Sciences (TWAS). Summary Agricultural Sciences Biology Chemistry Earth Sciences Engineering Sciences Mathematics Medical Sc ...

from the

Third World Academy of Sciences The World Academy of Sciences (TWAS) is a merit-based science academy established for developing countries, uniting 1,000 scientists in some 70 countries. Its principal aim is to promote scientific capacity and excellence for sustainable deve ...

(1990 and 1992), the Mexican Prize of Science and Technology (1999), the Rheimboldt-Hauptmann Prize of the University of São Paulo (2001) and the Péter Murányi Prize (2002). He was in the editorial board of several international journals, was foreign member of the U.S.

National Academy of Sciences The National Academy of Sciences (NAS) is a United States nonprofit, non-governmental organization. NAS is part of the National Academies of Sciences, Engineering, and Medicine, along with the National Academy of Engineering (NAE) and the Nat ...

. Ferreira was also a noted scientific leader in Brazil. He helped to found and is one of the editors-in-chief of the most influential international biomedical scientific journal, '' Brazilian Journal of Medical and Biological Research'', was a member of the Brazilian National Academy of Sciences and of the Brazilian Council of Science and Technology. He was founder and past president of the Brazilian Society for Pharmacology and Therapeutics and of the Brazilian Society for the Progress of Science (SBPC).

Bibliography

* Ferreira, S. H. 1972. Prostaglandins, aspirin-like drugs and analgesia. ''Nature New Biology''. vol. 240, p. 200-203. * Ferreira, S. H. and Nakamura, M. 1979. II-Prostaglandins hyperalgesia: the peripheral analgesic activity of morphine, enkephalins and opioid antagonists. ''Prostaglandins''. vol. 18, p. 191-200. * Ferreira, S. H., et al. 1988. Interleukin-1b as a potent hyperalgesic agent antagonized by a tripeptide analogue. ''Nature''. vol. 334, p. 698-700. * Ferreira, S. H., et al. 1991. The molecular mechanism of action of peripheral morphine analgesia: stimulation of cGMP system via nitric oxide release. ''European Journal of Pharmacology''. vol. 201, p. 121-122. * Ferreira, S. H., et al. 1993. Bradykinin initiates cytokine mediated inflammatory hyperalgesia. ''Brazilian Journal of Pharmacological Sciences''. vol. 110, p. 1227-1231. * Ferreira, S. H. and Lorenzetti, B. B. 1994. Glutamate spinal retrograde sensitization of primary sensory neurons associated with nociception. ''Neuropharmacology''. vol. 33, no. 11, p. 1479-1485.

Sources

* Adapted fro
Sérgio Henrique Ferreira Biography
Brazilian Academy of Sciences. {{DEFAULTSORT:Ferreira, Sergio Henrique 1934 births 2016 deaths Brazilian pharmacologists Members of the Brazilian Academy of Sciences Recipients of the Great Cross of the National Order of Scientific Merit (Brazil) University of São Paulo alumni People from Franca Foreign associates of the National Academy of Sciences TWAS laureates