Martin Schulz, head of the Department of Medicine of the Federal Union of German Associations of Pharmacists (ABDA), indicated that one of the most important changes in the pharmaceutical profession has been moving from a service focused on providing products to a service focused on patients with educational programs for users of the pharmacy and pay for advanced services. “.He has also highlighted that one of the areas of future treatment are ‘directed’ solutions, as the detection, prevention and solution of problems relating to drugs, with results for optimization of high-value products and upgrades to completion therapy.

In his speech, Schulz gave an example of two recent studies that have highlighted the important role of the pharmacist in the proper completion of treatment by patients, particularly in glucose self-monitoring of diabetes and therapy with inhaled asthma . In both cases, over 80% of patients did not meet their treatment correctly, whereas with the pharmacist’s intervention, this percentage was reduced by 40% and 30% respectively, demonstrating the important role of this professional .

The pharmacist must have as its main goal to be a pharmacy dispensing center and a center where there is a primary prevention and therapeutic monitoring of the patient, minimizing the possible adverse effects of drugs by an incorrect use by the patients. We can meet these goals by giving quality care, customer loyalty and implementing improvements in services.

It is an indispensable component of all cell membranes of animals. These are wrappers that are essential to protect the cell from its external environment (extracellular) and therefore helps keep the internal environment of the cell (intracellular).

It is a precursor of steroid hormones synthesized in the ovaries, testes and adrenal glands. Steroid hormones regulate essential processes in the body, such as growth and development of sexual characteristics.

It is a precursor of bile acids, which are important in digestion and absorption of fats.

Cholesterol Sources

In general, cholesterol comes from two sources: exogenous (dietary) and endogenous (synthesized in the body).

Cholesterol in your daily diet is a substantial source of total cholesterol and may contribute up to 20% to 40% of total cholesterol in the body. The small intestine is the site of cholesterol uptake from the diet. The endogenous synthesis accounts for 60% to 80% of the cholesterol. It is commonly accepted that the liver produced the bulk of endogenous colesterol. However, recent research indicates that much of the cholesterol biosynthesis takes place in non-hepatic tissues. The liver itself represents the majority of the uptake of cholesterol from plasma.

Plasma cholesterol

Plasma cholesterol (ie, blood cholesterol) is derived from both the endogenous and the exogenous cholesterol. The following actions in the body affect the level of cholesterol in the bloodstream:

Cholesterol biosynthesis

The main precursor for the biosynthesis of cholesterol and other lipids such as triglycerides and fatty acids is acetyl-coenzyme A or acetyl-CoA. The conversion of acetyl-CoA to cholesterol takes place in a complex way that requires 30 separate reactions.

While the primary product of this pathway is cholesterol, also important end products are formed. Ubiquinone is part of the electron transport chain of energy metabolism and dolicol is a component of cell membranes. Cholesterol itself is a component of cell membranes and a precursor to steroid hormones (eg cortisol, aldosterone, testosterone and estrogen) and bile acids.

Early and limiting step in the biosynthesis of cholesterol

The first series of reactions in the pathway of biosynthesis of cholesterol from the series of acetyl-CoA to 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) – is common for the synthesis of cholesterol and other lipids . The next step, the conversion of HMG-CoA to mevalonic acid, or mevalonate (MVA), is catalyzed by an enzyme called HMG-CoA reductase. This enzyme is known as the limiting enzyme reaction because this is a bottleneck in the biosynthesis pathway. The conversion of HMG-CoA, the substrate of HMG-CoA reductase, is the so called early and limiting step in the biosynthesis of cholesterol. Para reducir la conversión de HMG-CoA a MVA, debe inhibirse la acción de la HMG-CoA reductasa. To reduce the conversion of HMG-CoA to MVA, the action of HMG-CoA reductase should be inhibited.

Like the early and limiting step in the biosynthesis of cholesterol, the passage of the HMG-CoA reductase has a considerable biological importance. Several physiological signals act at the level of HMG-CoA reductase to reduce or increase the synthesis of cholesterol, depending on the needs of the organism. Por ejemplo, un nivel alto de colesterol libre en los hepatocitos significa que está presente una cantidad suficiente de colesterol; en respuesta, se inhibe la actividad de la HMG-CoA reductasa y se sintetiza menos colesterol. For example, a high level of free cholesterol in the liver means that this is a sufficient amount of cholesterol, in response it inhibits the activity of HMG-CoA reductase and cholesterol synthesis less. This process not only affects the amount of liver cholesterol, but also the amount of cholesterol in blood. In the liver, even small decreases in the production of cholesterol lead to an increase in the production of LDL receptors that remove cholesterol from the blood.

By the action of the enzyme HMG-CoA reductase, HMG-CoA is converted into mevalonic acid (MVA).

Absorción de colesterol Cholesterol absorption

Cholesterol absorption takes place in the small intestine. Cholesterol available for absorption comes from three sources:

Sources

Quantity (%)

1. Cholesterol in bile (biliary cholesterol). 50%

2. Cholesterol in the diet (exogenous). 31%

3. Cholesterol in the scaly epithelial cells of the intestinal wall during normal cell turnover. 19%

Of total cholesterol available for absorption, 50% is absorbed through the intestinal wall and 50% is excreted in feces.

The mechanism by which cholesterol is absorbed from the intestine is complex and only partially understood. Studies suggest that cholesterol is emulsified by bile salts, wrapped in micelles and transferred to the brush border of the small intestine. After entering the enterocytes (cells in the intestinal mucosa). Once inside the cells, cholesterol is esterified (combined with a fatty acid) through the action of the enzyme called acyl-coenzyme A: cholesterol aciltransferasa (ACAT) and assembled into chylomicrons. These chylomicrons are secreted into the lymph and subsequently enter the blood. By inhibiting cholesterol absorption through the intestinal wall, ie by increasing the amount of cholesterol excreted, the amount of cholesterol entering the blood within these chylomicrons will be reduced.

Conclusion

Cholesterol fulfills three important functions in the body: it is an essential component of cell membranes of animals, is a precursor of steroid hormones and is a precursor of bile acids.

Cholesterol is derived from the diet (exogenous) and biosynthesis (endogenous).

Cholesterol in daily diet, bile and epithelial cells are absorbed through the small intestine. By inhibiting cholesterol absorption in the intestine plasma cholesterol can be reduced.

The limiting enzyme in the biosynthesis of cholesterol called HMG-CoA reductase catalyzes the conversion of HMG-CoA to mevalonic acid (mevalonate).

Of these, at this time, only about 80,000 have some therapeutic use. Currently drugs are obtained by four different methods: a) chemical synthesis, b) biosynthesis, c) from natural products, and d) biotechnology. However, it is often used as mixed processes, eg with certain antibiotics (macrolides) or antifungals (Echinocandins), which combines chemical synthesis to biosynthesis to improve the microbiological activity orits pharmacokinetic characteristics.In other occasions, some active ingredients extracted from natural products are modified by semi-synthesis reactions to complete its structure and improve its business or its pharmacokinetic characteristics. Thus, precursors of anovulatory or anti-inflammatory steroids, from plants of the genus Dioscorea and Solanum, are amended later by methods of semi-synthesis or biosynthesis to produce various medicines.  Finally, some proteins produced by recombinant technology (interferons, G-CSF, erythropoietin, etc..) are chemically modified by chemical synthesis to improve their bioavailability or delay its clearance.

Drugs derived from biotechnology are emerging in a therapeutic class that presents differential clinical features , not only by their origin, but also by their chemical structure and some pharmaceutical and pharmacological properties.

Although modern biotechnology was born in 1953 when the structure of deoxyribonucleic acid (DNA) was discovered, its incorporation to human therapeutics does not occur until the early 80s with the use of insulin and recombinant growth hormone in hormone replacement therapy . To do this some technological advances were required like the introduction of restriction enzymes by Paul Berg in 1973, and cloning of genes for human insulin, developed by Herber Boyer in 1978.

Until 1996, the incorporation of recombinant drugs is largely anecdotal, that situation changed radically in the last decade, reaching a spectacular development. Nowadays there have been incorporated into the therapeutic arsenal about a 100 different kinds of medicines, although about 700 molecules for the diagnosis and treatment of some 250 diseases, found in 2005 in different phases of clinical research.

Several reports agree that biotech drugs come to represent in the future between 20-25% of all the medications. Since 2002, the percentage of new biotech molecules allowed in the U.S. exceeds the corresponding molecules from other sources, mainly the chemical synthesis.

Carlos Cusirramos Dueñas

Structurally, the virions are irregular spherical particles with a diameter of approximately 100 nm (80 to 120 nm), covered by a lipid membrane in the looming glycoproteins hemagglutinin (H) and neuraminidase (N).

Immunity against the flu represent virus antibodies against the H antigen, whereas antibodies against N antigen reduce the spread of the virus.

In type A, the inside of the virion is composed of eight genome segments of viral RNA single strand that encode all the proteins and allows the possibility of a different grouping of genes during infection leading to mutations. These variations are the difficulty in the immunization of the host.

The most common factors for failure in clinical research include: lack of efficacy, doubts about the clinical safety and negative results toxicological in preclinical evaluation.

Among the objectives of the areas of efficiency and safety it has been prioritized to enhance the capabilities of clinical trials and intensify dialogue with the authorities to reduce time and costs of clinical development, and improvement in patient recruitment. Thus has begun the clinical research setting in motion Best Project, as a platform for excellence in clinical research.

It is required full participation of the hospital pharmacists in the discussion of the protocol both in its development with the developer, as before submission.

Means of communication between the pharmaceutical sponsor researches should increase, delving into the production, management and control samples. As a result of this coordination a more direct relationship with the patient by providing better information on issues related to compliance with the protocol and adverse events should be promoted.

We are talking about ghrelin, a small protein that regulates food intake, increased levels of anxiety and, as findings at the National University of Cordoba (UNC) also optimizes memory. This evidence now opens a route to finding drugs able to modify those processes.

Seven years ago it was discovered that the ghrelin, also called “the hunger hormone”, is closely related to the start of food intake, and it was confirmed that before meals high levels of this peptide (small protein)are present. Many scientific studies were conducted on the topic, especially those intended to find the function and the possible role of this substance in the origin and treatment of obesity and anorexia.

By having the certainty that ghrelin modulates hunger, a group of researchers from the School of Chemical Sciences, led by Susana Rubiales, Professor of Human Physiology, Department of Pharmacology of the academic unit, decided to investigate the relationship between food intake , anxiety and memory.

For this reason, subsequent experiments performed consisted of injecting the substance in the central nervous system of laboratory rats and measuring the three processes. What was the outcome? As expected, they found that when they enter the body, both ghrelin increased hunger of the animals as their levels of anxiety.

“The surprise was discovering the improvement of memory,” says project manager and explains that to assess the phenomenon, it was necessary to perform various tests that showed an “evident increase” in withholding information from the past.
Rubiales emphasizes that their work is “basic research” and that they are trying to explain how the central nervous system modulates substance intake, anxiety and memory from models with behavioral experiments in laboratory rats and different biochemical determinations. However, she stresses that, although the research is missing several steps for it to have a theurapeutic utility in humas, thanks to rapid advances in the production of drugs they will soon be able to “stimulate or inhibit the receptors of  ghrelin and, somehow, modular behavior”.

In this regard, the scientist says that finding new drugs for the treatment of obesity, anorexia, bulimia and other eating disorders is a priority among the different research areas of the pharmaceutical industry.
Why link food intake with memory?

The habit of eating and drinking is an important space in the daily lives of people. Therefore, there are many opportunities for information related to time spent eating to be processed and then be able to influence decisions about what, when and how much you eat food.

Rubiales so argues the importance of linking the two behaviors, which adds: “We hypothesize that the representation in memory of the information related to meals eaten in the recent past is a factor that influences the consumption retrospectively, so that manipulating the memory of an episode of intake would be obtained on the effect of reducing the subsequent consumption. ”
Meanwhile, according to the professor, the possibility that ghrelin or its antagonists can be used as potential therapeutic agents in some disorders associated with food intake (obesity, anorexia or bulimia), derives from the assumption that these drugs could modify “not only intake but also some of the emotional turmoil that accompany certain diseases.”

The “hunger hormone” in action

Ghrelin is synthesized in the stomach and the central nervous system. In the first case, the route that it follows within the body is simply going via the blood to a structure called the hypothalamus, where the main nerve cells that regulate intake are located. For its part, the central nervous system also releases the substance when there is a feeling of hunger.

Apart from the evidence that this small protein acts at the hypothalamus and modulates the intake, the university scientists found out that ghrelin also operates in other central nervous system structures (amygdala, hippocampus and dorsal raphe nucleus) that are related with intake, anxiety and memory.

“By injecting the drug in these three structures, we saw that in addition to increasing the food intake and anxiety, it also improved memory,” says Rubiales.

Currently, researchers are continuing the project by analyzing the mechanisms that justify why ghrelin produces certain changes in behavior.