Química Medicinal: 25 anos de planejamento racional de fármacos

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The Sociedade Brasileira de Química is commemorating its 25th anniversary, and this paper is intended to draw an overview of the Brazilian Medicinal Chemistry over all these years. In 1977 Brazil had almost no activities at all in the field, albeit many efforts were already on the way for encouraging Brazilian Scientists to enter the area. Among many different endeavours to help medicinal chemists to fulfil their proposals and the establishment of an on-going research with the help of networks, the Sociedade Brasileira de Química created, in 1991, its own Division on Structure and Activity Relationship, which became the Division of Medicinal Chemistry, in 1997.

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Relationship between oral glucose tolerance and gastric emptying in normal healthy subjects.

Adrie Straathof, Peter M Edelbroek, Michael Horowitz … (1993)

The relationships between gastric emptying and intragastric distribution of glucose and oral glucose tolerance were evaluated in 16 healthy volunteers. While sitting in front of a gamma camera the subjects drank 350 ml water containing 75 g glucose and 20 MBq 99mTc-sulphur colloid. Venous blood samples for measurement of plasma glucose, insulin and gastric inhibitory polypeptide were obtained at--2, 2,5,10,15,30,45,60,75,90,105,120 and 150 min. Gastric emptying approximated a linear pattern after a short lag phase (3.3 +/- 0.8 min). The 50% emptying time was inversely related to the proximal stomach 50% emptying time (r = -0.55, p < 0.05) and directly related to the retention in the distal stomach at 120 min (r = 0.72, p < 0.01). Peak plasma glucose was related to the amount emptied at 5 min (r = 0.58, p < 0.05) and the area under the blood glucose curve between 0 and 30 min was related to the amount emptied at 30 min (r = 0.58, p < 0.05). In contrast, plasma glucose at 120 min was inversely related to gastric emptying (r = -0.56, p < 0.05) and plasma insulin at 30 min (r = -0.53, p < 0.05). Plasma insulin at 120 min was inversely related (r = -0.65, p < 0.01) to gastric emptying. The increase in plasma gastric inhibitory polypeptide at 5 min was related directly to gastric emptying (r = 0.53, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

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Hyperglycaemia slows gastric emptying in type 1 (insulin-dependent) diabetes mellitus.

B Chatterton, Alasdair R Fraser, Simon Harding … (1990)

In 10 patients with Type 1 (insulin-dependent) diabetes mellitus gastric emptying of a digestible solid and liquid meal was measured during euglycaemia (blood glucose concentration 4-8 mmol/l) and during hyperglycaemia (blood glucose concentration 16-20 mmol/l). Gastric emptying was studied with a scintigraphic technique and blood glucose concentrations were stabilised using a modified glucose clamp. Patients were also evaluated for gastrointestinal symptoms, autonomic nerve function and glycaemic control. When compared to euglycaemia, the duration of the lag phase before any of the solid meal emptied from the stomach (p = 0.032), the percentage of the solid meal remaining in the stomach at 100 min (p = 0.032) and the 50% emptying time for the solid meal (p = 0.032) increased during hyperglycaemia. The 50% emptying time for the liquid meal (p = 0.042) was also prolonged during the period of hyperglycaemia. These results demonstrate that the rate of gastric emptying in Type 1 diabetes is affected by the blood glucose concentration.

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UK Prospective Diabetes Study (UKPDS). VIII. Study design, progress and performance.

(1991)

The UK Prospective Diabetes Study (UKPDS) is a multi-centre, prospective, randomised, intervention trial of 5100 newly-diagnosed patients with Type 2 (non-insulin-dependent) diabetes mellitus which aims to determine whether improved blood glucose control will prevent complications and reduce the associated morbidity and mortality. Newly presenting Type 2 diabetic patients aged 25-65 years inclusive, median age 53 years, median body mass index 28 kg/m2 and median fasting plasma glucose 11.3 mmol/l, were recruited and treated initially by diet. Ninety five percent remained hyperglycaemic (fasting plasma glucose greater than 6 mmol/l) and were randomly allocated to different therapies. In the main randomisation, those who were asymptomatic and had fasting plasma glucose under 15 mmol/l were allocated either to diet policy, or to active policy with either insulin or sulphonylurea aiming to reduce the fasting plasma glucose to under 6 mmol/l. Over 3 years, the median fasting plasma glucose in those allocated to diet policy was 8.9 mmol/l compared with 7.0 mmol/l in those allocated to active policy. The Hypertension in Diabetes Study has been included in a factorial design to assess whether improved blood pressure control will be advantageous. Patients with blood pressure greater than or equal to 160/90 mm Hg were randomly allocated to tight control aiming for less than 150/85 mm Hg with either an angiotensin-converting enzyme inhibitor or a Beta-blocker or to less tight control aiming for less than 200/105 mm Hg. The endpoints of the studies are major clinical events which affect the life and well-being of patients, such as heart attacks, angina, strokes, amputations, blindness and renal failure. To date, 728 patients have had at least one clinical endpoint. Surrogate endpoints include indices of macrovascular and microvascular disease detected by ECG with Minnesota Coding, retinal colour photography and microalbuminuria. The studies also aim to evaluate potential risk factors for the development of diabetic complications such as smoking, obesity, central adiposity, plasma LDL- and HDL-cholesterol, triglyceride, insulin, urate and other biochemical variables. The studies are planned to terminate in 1994, with a median follow-up of 9 years (range 3-16 years) for the glucose study and 5 years (range 2-6 years) for the hypertension study.

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Author and article information

Contributors

Antonia Tavares do Amaral: Role: ND

Carlos Alberto Montanari: Role: ND

Journal

Journal ID (publisher): qn

Title: Química Nova

Abbreviated Title: Quím. Nova

Publisher: Sociedade Brasileira de Química (São Paulo )

ISSN: 1678-7064

Publication date (Print): May 2002

Volume: 25

Issue: suppl 1

Pages: 39-44

Affiliations

[1 ] Universidade de São Paulo Brazil

[2 ] Universidade Federal de Minas Gerais Brazil

Article

Publisher ID: S0100-40422002000800008

DOI: 10.1590/S0100-40422002000800008

SO-VID: 25c843fd-794f-449a-b218-7b4f853d16ad

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http://creativecommons.org/licenses/by/4.0/

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SciELO Brazil

Self URI (journal page): http://www.scielo.br/scielo.php?script=sci_serial&pid=0100-4042&lng=en

Química Medicinal: 25 anos de planejamento racional de fármacos Translated title: 25 years of medicinal chemistry in Brazil

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Most cited references 96

Relationship between oral glucose tolerance and gastric emptying in normal healthy subjects.

Hyperglycaemia slows gastric emptying in type 1 (insulin-dependent) diabetes mellitus.

UK Prospective Diabetes Study (UKPDS). VIII. Study design, progress and performance.

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