Beat Drug Testing, Clean Urine Drug Test, Drug Detox Kit, Hair Follicle Drug Test False Positive, Home Urine Drug Test

Why Shampoos Could Be The Most Dangerous Cosmetic Products?

Drugstestproduct — Fri, 20 Aug 2010 04:15:27 +0000

Cosmetic and medical products that get in contact with our skin are absorbed through the skin, get in the blood stream and can accumulate in high quantities in different parts of our bodies. The absorption of substances from outside the skin to positions beneath the skin, including entrance to the blood stream, is referred to as Percutaneous Absorption. Usually, shampoos contain very aggressive cleaning ingredients that desroy hydrolipidic film. Hydrolipidic film is an emulsion of water (hydro) and fat (lipos). Its main function is an external barrier, a defense against bacteria and fungi. In addition it keeps the skin supple. The cleaning ingredients of shampoos destroy external barrier of the scalp and all the dangerous ingredients found in shampoos enter our bodies.

This is why all cosmetic products not just medical products must be tested for safety.

Hairdressers and estheticians are considered to be at high professional risk, because they come in contact with cosmetic products more than anyone else. Most importantly, there are a lot of different ingredients in cosmetic products, especially shampoos that can be very damaging to our health. In particular, there are lot of ingredients widely used in the cosmetic industry that are not being studied as much as food products and drugs, but they can be very dangerous and carcinogenic (can cause cancer). The Australian Institute of Health and Welfare says the number of cancers being diagnosed each year is growing faster than the overall population. Skin cancer has increased by more than 350% in last five years.

This is why all Allatolia products have been extensively tested and analyzed for safety and clinical effectiveness.

Allatolia products are manufactured without the addition of colorings, perfumes, and thickening ingredients since their origin (1978), because the very high quality of raw materials used allows avoiding any kind of covering. Colors and perfumes are often added to products in order to cover bad quality of raw materials (low quality raw materials often smell very bad). Dermatologists and Allergologists consider perfumes and colors which are added to cosmetic products as the most responsible for contact dermatitis. Contact dermatitis is a localized rash or irritation of the skin caused by contact with a foreign substance. Professionals in the cosmetic field, especially hairdressers are at higher risk for developing irritations and allergic reactions due to the fact that they use cosmetic products all day long.

Allatolia products are made without formaldehyde since the origin (1978). Formaldehyde (or formic aldehyde) is a preservative considered to be very dangerous, although widely used for its low price. Formaldehyde is classified as a probable human carcinogen by the U.S. Environmental Protection Agency. International Agency for Research on Cancer states that there is sufficient evidence that formaldehyde causes nasopharyngeal cancer in humans. Formaldehyde also causes allergies.

Under certain dosage the present laws do not yet force producers to declare the presence of formaldehyde. In Switzerland the use of formaldehyde is forbidden for both medicines and cosmetics since 1967. Therefore, the voluntary procedure to submit the products to the composition exam to the laboratories of Swiss Hygiene and the consequent certification of conformity means that, under precise responsibility of the producer, the products are made without formaldehyde. All the certificates that state that all Allatolia products do not contain formaldehyde can be found on our website.

Villa Bofghini products are manufactured without Methylene Chloride since the origin (1978). Methylene Chloride has always been considered as a very dangerous substance for human health. In spite of this, it has been largely used to manufacture hair sprays and hair fixing products mainly because of its low cost and of its high volatility characteristic (it is able to let the other ingredients exhale very quickly, thus allowing to fix hair almost immediately). Obviously, Methylene Chloride and other substances heavily pollute the environment. This bears dangerous consequences to the health of people using such toxic products. Only in 1998 did the European Commission finally classify it as “R-40″ meaning dangerous substance able to cause irreversible noxious effects to human health.

Allatolia products have been clinically studied and tested for maximum safety by Repeated Insult Patch Test. All Allatolia products have passed this test. Under normal conditions it takes 28 days for the basal layer of skin cells through their death and physiological transformation to finally reach the skin surface. This is the cycle of the skin, called cellular turnover. This is what allows the skin to have the power of self-defense form anything that comes in contact with it.

There are two clinical-pharmacological tests used to evaluate safety of products for topical application. They are Patch Test and Repeated Insult Patch Test. The Patch Test usually lasts 48 hours. As previously explained, the cellular turnover of the skin lasts 28 days. This means that the product tested only for 2 days cannot be called hypoallergenic, because 2 days are not enough to really test the product. The Repeated Insult Patch Test lasts for 30 days, that is to say two more days of the skin cellular turnover. This is why the product that managed to over come such a rigid test is certified as “Incapable of causing irritation or allergic reactions”.

According to the FDA, there are no Federal standards or definitions that govern the use of the term “hypoallergenic”. The term means whatever a particular company wants it to mean. Manufacturers of cosmetics labeled as hypoallergenic are not required to submit substantiation of their hypoallergenicity claims to FDA.

Allatolia products have overcome the strictest clinical-pharmacological test in the University Laboratories for Maximum Safety: “The Repeated Insult Patch Test”. All Allatolia products are certified as incapable of causing irritation or allergic reactions.

Up to today, Allatolia is the unique whole range of products in the world that was able to overcome the hardest test for maximum safety.

The scalp is at the top of the list among the body parts affected by Allergenic Contact Dermatitis. Shampoos are the most dangerous products, because they destroy the hydrolipidic film of the skin (extreme barrier for the protection of the skin) and that provokes the dangerous rebound effect of the sebaceous gland, and in turn canceling the skin power to self-defense. That is why they are considered to be the most dangerous cosmetic products. For this reason hairdressers are at a higher risk.

Allatolia finished products have been registered and approved by the FDA. The finished product is the result of mixing together various ingredients. Every ingredient has its own characteristics which can be changed by combining it with another ingredient. It is evident that by advertising a product only because it contains a particular ingredient does not show the proved scientific value of the finished product. So, it is very important to test the finished product as well as each ingredient separately. All ALLATOLIA products have been tested as finished products.

For most shampoos, the manufacturing process starts with making a large amount of concentrated shampoo in one shot, and then it is diluted. Allatolia, on the other hand manufactures their shampoos differently. We do it by addition of ingredients to each bottle one by one. We add the ingredients, not dilute a high concentrated solution.

According to the results of the tests and analysis of Allatolia products, the use of Allatolia products allows achieving important clinical results with no side effects.

The whole range of Allatolia products has very advanced scientific characteristics, because we are able to achieve both aesthetic and curative results simultaneously. This is another scientific and technical innovation called Product Dynamism.

The unique distinctive characteristics of Allatolia line shows that Allatolia manufacturing levels and quality of the ingredients were almost 30 years ahead of the modern European Regulations.

Importance of Testing on Pharmaceutical Drugs Weighs True Says Trasylol Attorney

Drugstestproduct — Mon, 16 Aug 2010 12:15:46 +0000

The drug Trasylol, manufactured by Bayer Pharmaceuticals is a great example of the poor testing standards that the medical industry currently exudes. Trasylol was a popular drug used in heart bypass surgeries to control the amount of bleeding. However it was found that Trasylol directly caused kidney complications and failure in those who were administered the drug. Bayer did their own study of the side effects of the drug finding the kidney complications to hold true however they decided not to make this study public. Therefore for two years Bayer allowed Trasylol to remain on the market knowing that it caused kidney complications and failure. The FDA was not given this information until two years after Bayer did their study when a private study was done that finally released the information. The fact of the matter is that Bayer knowingly withheld the negative side effects, allowing innocent patients to incur these complications. Over 20,000 deaths were determined to have occurred from the time that Bayer did their study to the time that Trasylol was finally recalled.

The ethical issues involved with this case are extremely indicative of the way that the pharmaceutical drug industry conducts business. Everything is about revenues and in the way that a certain drug performs on the market. If a drug is doing well then it will be protected at all costs despite the risks associated with the drug. Trasylol attorneys have seen this trend in the pharmaceutical market for decades due to past occurrences. It is a shame that an industry focused on profits is the one that most directly affects the life of every single American. You would think that an industry involved in the well being of American citizens would weigh heavy the importance of their actual health. In order to turn around this industry an importance needs to be placed on the quality of its products. Pharmaceutical drugs must go through rigorous testing and quality control processes to ensure that no negative findings will be found in the form of unknown negative side effects.

New standards and regulations must be made in order to ensure the safety of a new product. This will make sure that these new drugs will only be introduced onto the market when it is known that all testing has been done and that all requirements have been met. Crossing new thresholds in the medical industry involved new and creative ideas and thinking, but it is not worth the benefit if compliances are not met. In order to establish these new rules, the pharmaceutical industry my first assess the way that practice ethics. For the basis of new ideas must stem from the right way of thinking. If you have been caused harm from being administered Trasylol, contact a Trasylol attorney immediately. A Trasylol attorney has the experience and knowledge in dealing with large pharmaceutical and insurance companies. Don’t let another conglomerate take advantage of their position in the market and contact a Trasylol attorney today.

Rapid Response® Drugs of Abuse Tests

Drugstestproduct — Sat, 14 Aug 2010 10:09:41 +0000

Toronto, Canada – BTNX Inc. has launched a series of Rapid Response® advanced FDA approved in-vitro diagnostic drugs of abuse tests, which are used for home, professional and corporation point of care drugs of abuse testing.

The drug tests can easily detect any of Amphetamine, Barbiturate, Benzodiazepine, Buprenorphine, Cocaine, Ecstasy, EDDP (Methadone Metabolite), Heroin, Marijuana, Methadone, Methamphetamine, Morphine, Opiate, Oxycodone, Phencyclidine, Propoxyphene, Tricyclic Antidepressant. Or any combinations range from 1 test panel to 12 test panels.

Rapid Response ® drugs of abuse test series includes urine drug test cups, urine drug test panels, urine drug test strips, urine drug test cassettes, saliva drug tests and lab hair drug tests.

Rapid Response® branded are trusted by professionals in laboratories, physicians’ offices, hospitals and clinics worldwide for their diagnostic testing requirements.

For more information about the products please visit http://www.BTNX.com , or contact Sales@BTNX.com.

Toronto, Canada – BTNX Inc. has launched a series of Rapid Response® advanced FDA approved in-vitro diagnostic drugs of abuse tests, which are used for home, professional and corporation point of care drugs of abuse testing.

The drug tests can easily detect any of Amphetamine, Barbiturate, Benzodiazepine, Buprenorphine, Cocaine, Ecstasy, EDDP (Methadone Metabolite), Heroin, Marijuana, Methadone, Methamphetamine, Morphine, Opiate, Oxycodone, Phencyclidine, Propoxyphene, Tricyclic Antidepressant. Or any combinations range from 1 test panel to 12 test panels.

Rapid Response ® drugs of abuse test series includes urine drug test cups, urine drug test panels, urine drug test strips, urine drug test cassettes, saliva drug tests and lab hair drug tests.

Rapid Response® branded are trusted by professionals in laboratories, physicians’ offices, hospitals and clinics worldwide for their diagnostic testing requirements.

Dilaudid: Prescription Drug Abuse & Testing

Drugstestproduct — Fri, 06 Aug 2010 13:52:56 +0000

Dilaudid is the trade name of hydromorphone hydrochloride which is a hydrogenated ketone of morphine that is used as an opioid analgesic to treat moderate to severe pain. White coat clad chaps call it 4, 5?-epoxy-3-hydroxy-17 methylmorphinan-6-one hydrochloride in their language.

Some bacteria have been shown to be able to turn morphine into hydromorphone. As reported in the July 1993 issue of Applied Environmental Bacteriology, the bacterium Pseudomonas putida, serotype M10, a naturally occurring NADH-dependent morphinone reductase which lives in an aqueous solution containing morphine, forms a significant amount of hydromophone as an intermediary metabolite. Same way, codeine may also be turned into hydrocodone.

Dilaudid Prescription, Dosage & Administration:

Dilaudid, a narcotic analgesic, is prescribed drug for the relief of moderate to severe pain due to biliary colic (pain caused by an obstruction in the gallbladder or bile duct), burns, cancer, heart attack, injury (soft tissue and bone), renal colic (sharp lower back and groin pain usually caused by the passage of a stone through the ureter) & surgery etc.

Hydromorphone comes as a tablet and also in liquid form & thus can be taken orally. It also comes as a rectal suppository. Each 5 ml of Dilaudid oral liquid usually contains 5 mg of hydromorphone hydrochloride. In addition, other ingredients may include purified water, methylparaben, propylparaben, sucrose, and glycerin. Dilaudid oral liquid may contain traces of sodium metabisulfite. Although, dosage is adjusted by physician according to the severity of the pain and the response of the patient, however, frequently, oral forms are taken every 4-6 hours while the suppository is usually used every 6-8 hours.

Dilaudid Abuse:

Hydromorphone has been observed to be one of those habit-forming drugs. Hydromorphone is largely abused in US and is subject to criminal diversion. So, you should never take a larger dose than what is prescribed by your physician. Taking it more often or for a longer period than what your doctor tells you to is equally harmful and must be avoided at all costs.

Effects of Dilaudid Abuse:

Adverse effects of hydromorphone i.e. Dilaudid are similar to those of other opioid analgesics, and represent an extension of pharmacological effects of the opioid drug class. The major hazards of hydromorphone include respiratory and CNS depression. The most frequently observed adverse effects are sedation, nausea, vomiting, constipation, lightheadedness, dizziness and sweating.

Physical Dependence on Dilaudid:

Opioid analgesics such as Dilaudid may cause psychological and physical dependence. Physical dependence results in withdrawal symptoms in patients who abruptly discontinue the drug. Physical dependence usually does not occur to a clinically significant degree until after several weeks of continued opioid usage, but it may occur after as little as a week of opioid use. Physical dependence and tolerance are separate and distinct from abuse and addiction.

Miscellaneous:

If you are sensitive to or have ever had an allergic reaction to Dilaudid or narcotic painkillers, you should not take this medication.

To limit abuse of opioid drugs like Dilaudid it is necessary to properly assess the patient, employ proper prescription practices, periodically re-evaluate the opioid therapy, and properly dispense and store the drugs.

Demerol Testing:

As with other drugs, a diverse array of techniques is available to test for Dilaudid abuse. As anticipated, some amount of Dilaudid remains unchanged while rest of it forms different metabolites.

These unchanged Dilaudid or Dilaudid derivatives and their metabolized products can be detected using any of the following methods:

•Urine based Dilaudid/metabolite testing

•Hair follicle based Dilaudid/metabolite detection

•GC based Dilaudid/metabolite detection

•Mass spec based Dilaudid/metabolite testing

•Dilaudid/metabolite-specific antibody based diagnostic kits

Glucose (urine) Tests-drug

Drugstestproduct — Mon, 19 Jul 2010 04:54:49 +0000

How the Drug Works

Glucose does not normally appear in the urine, but when too much glucose builds up in the blood, the excess spills over from the kidney into the urine where it can be detected by specially designed plastic test strips and reagent tablets containing chemicals which detect glucose in urine. Color changes occur according to the amount of sugar present.

Regular monitoring of glucose levels aids in the control of diabetes. It will help determine medication, exercise and dietary needs and help decrease complications (eg, kidney and eye problems) and problems during pregnancy.

Ketones appear in the urine when the body breaks down body fats to use as a source of energy or food. This can occur in fasting individuals, outof-control diabetics and individuals on starvation diets. Proteins in the urine may be an early sign of kidney disease.

Uses

To detect glucose in urine.

To aid diabetics in monitoring medication regimens, diet and exercise programs.

To help prevent the development of complications and problems during pregnancy.

Avoid contact with skin, mucous membranes or clothing. If contact occurs, flush the affected area with large amounts of water. If test strips, tape, or tablets are eaten or rubbed in the eyes, contact your doctor or local poison control center immediately. If eaten, do not induce vomiting; instead, drink large amounts of water or milk. If contact with the eyes occurs, flush with water for 15 minutes. Get prompt medical attention.

Specimen Collection and Handling: Collect fresh urine in a clean, dry container and test as soon as possible. (An alternate method is to pass the test strips directly through the urine stream). If testing cannot be done within an hour after collection, refrigerate. Let it return to room temperature before testing. Prolonged exposure of unpreserved urine to room temperature (59° to 86°F) may result in bacterial contamination and bacterial consumption of the glucose. Urine preservatives may also affect the accuracy of test results.

Storage and Handling: For bottled strips-Store at room temperature (59° to 86 F). Do not store the bottle in direct sunlight. Protect from light, heat, and moisture.

Keep unused test strips in the original bottle with the cap tightly closed. Always replace the cap immediately and tightly. A new bottle of test strips can be used for 6 months after first being opened. Always write the date you first opened the bottle on the bottle label. Do not use the product after the expiration date. Use of strips beyond the expiration date may yield inaccurate test results. Never transfer strips to another bottle. Do not remove drying agent from the bottle. The agent absorbs moisture and keeps the strips dry. Never put cotton or other materials in the bottle. If test areas are discolored or darkened, throw the strip away and use a strip from a new bottle.

For tablets – Tablets have prolonged stability in the unopened container if stored at room temperature between 59° and 86°F. Do not refrigerate. Do not store in direct sunlight. Once the bottle is opened, protect from moisture. Excessive moisture may cause a chemical reaction and a bottle explosion may occur. Use tablets on a regular basis and do not store for extended periods of time after the bottle is opened. Recap the bottle tightly immediately after removing a tablet. Tablets in foil must be used immediately upon opening. Protect tablets from light, heat and moisture. Do not open the bottle in a steamy bathroom. Moisture causes tablets to turn a deeper shade of blue. If tablets darken or if test results seem questionable or inconsistent with expected findings:

Confirm that product is within expiration date shown on label or foil. Check performance with a positive control. If proper result is not obtained, discard and retest with a fresh tablet.

Tablets: Sugars other than glucose will cause a positive test result. These sugars include: Lactose, fructose, galactose, and pentose.

Ketones: High levels of ketones may cause false positive test results for urine containing small amounts of glucose.

Drug Interactions

Tell your doctor or pharmacist if you are taking or planning to take any overthe-counter or prescription medication or dietary supplements while testing for urine glucose. The following drugs and drug classes may interact with the test to cause questionable results:

Aspirin (large amounts)

Riboflavin

Nalidixic acid (Neg Gram)

Sulfa drugs (eg, sulfonamides)

Nitrofurantoin (eg, Furadantin)

Vitamin C (ascorbic acid)

Phenazopyridine (eg, Pyridium)

Guidelines for Use

Follow instructions on the label exactly.

Glucose is not normally detected in urine.

Monitor urine for glucose and ketones as prescribed. Monitor urine ketones if your blood glucose level has been greater than 300 mg/dL for 2 consecutive blood glucose determinations. Blood glucose monitoring is recommended to achieve normal blood sugar levels. Keep track of your blood glucose results so that adjustments in your treatment program can be made more easily.

Participate in a thorough diabetes education program so that you understand diabetes and all aspects of its treatment, including diet, exercise, personal hygiene, and how to self-monitor blood or urine glucose.

Diabetics – Monitor glucose: When you have a cold, the flu or any other kind of illness. When you “feel” the signs of high blood sugar (more than 240 mg/dL) or when your blood sugar is well over the range your doctor has set for you (if you do blood glucose monitoring).

When you are under unusual physical or emotional stress.

During pregnancy after a testing pattern has been established with your doctor or educator.

Have all the materials you need before beginning the test: Test strips, timer (stopwatch or watch with a second hand), and a clean dry container.

Color vision is needed to properly read test results. Have someone else confirm the test results if in doubt.

If test results seem questionable, check expiration date on the label, repeat the test using a new test strip or tablet and a fresh urine specimen.

If your are unable to identify the cause of a low or high test result, contact your doctor or diabetes educator. Know the symptoms of hypergly cemia (high blood sugar), which include thirst, hunger and frequent and excessive urination and those of hypoglycemia (low blood sugar), which include trembling, sweating, blurred vision, rapid heartbeat, and tingling or numbness around mouth or fingertips.

Individuals with high uric acid, bilirubin cholesterol, triglyceride, or hematocrit levels may have lowered glucose levels.

Diabetes education may be obtained through your local chapter of the American Diabetes Association.

Some of these items can cause burns. Avoid contact with skin, eyes, mucous membranes, and clothing. Keep away from children.

Drug Development and Discovery in an Industrial Context

Drugstestproduct — Sat, 03 Jul 2010 09:07:42 +0000

Preface

A growing industrial demand for high throughput screening of new molecular entities (NME) has spurred great advances in various divisions of scientific development. Researchers has begun to combine various scientific methods to meet the competitive demands in modern drug development, and as a consequence optimized individual phases of drug development.

Technological improvements should ensure high quality expeditious drug development and a as a consequence a modern “fast track” from drug discovery to marketed product.

These scientific advances should however be viewed in sharp contrast to the increased economical expenditures observed in pharmaceutical companies worldwide. The price from discovery phase to actual marketing is estimated to be in the region of 0.8 billion to 1.7 billion dollars (11) and research has shown that investments in NME’s has increased 55 % over the last five year (12). These economical prospects are paradoxically followed by the fact that there has been observed a mere 7% increase in FDA-approved NME’s from 1993 to 2003. These combined factors are inherently linked to a new paradigm shift in drug development where technological advances outrun the collaborative marketing of new drugs.

This project will present the reader with three established analytical methods in drug development and link these methods with nine analytical properties proposed by M. Valcárel and A. Rios (2). Implementation of these methods in drug development and individual quality standards and guidelines will be presented and discussed and the project will be summarised with concluding remarks.

The nine analytical properties

The analytical properties proposed by M. Valcárel and A. Rios (2) should be regarded as a framework which efficiently introduces the students to the various aspects of analytical chemistry. They are a means of providing a hierarchical approach toward the analytical chemistry curriculum and should ensure an organized introduction to analytical chemistry.

The significance of introducing analytical properties hierarchically to students can be described in terms of the following three groups proposed by the authors. The most important group is the top or capital group. This group is defined by the need for accurate and representative data which in turn is the sole contributor towards the quality of the results.

The second group, the basic properties, ensure the quality of the analytical process and cover the more practical aspects of analytical chemistry. They include such properties as selectivity, precision, sensitivity and proper sampling. They are properties which during the course of an analytical approach can prove contradictory and could lead to a great deal of decision making in the process. The decisions which are made could alter the quality of the analytical processes and in turn influence the quality of the results. The scientist must reflect on these basic properties and establish a standard by which the analytical processes are conducted in order to facilitate high quality analytical processes. The various analytical factors their complementary and contradictory relationships (2) fig. 4) should be evaluated and the analytical research should be conducted accordingly.

The quality of the analytical process and the quality of the results are thus highly dependent on one another, and it should become apparent that the capital properties and the basic properties have a mutual relationship in obtaining high quality results meeting external quality standards. The accuracy and representativeness defined by the capital properties is only relevant if we ensure strict precision, sensitivity, selectivity and proper sampling in the laboratory.

The last group of properties, the accessory properties, are interesting in respects to their mutual influence and relationship with the basic properties. The accessory properties are represented by expeditiousness, cost-effectiveness and personnel safety and comfort. These are properties reflecting the competitive aspects of analytical chemistry and are mutually dependent on the basic properties. Thus, compromises regarding sensitivity, precision and selectivity could yield greater expeditiousness and improved productivity compared to competing companies or laboratories. There are however contradictory aspects of the accessory properties and reducing the basic properties could potentially influence various accessory properties thus leading to further challenges in the productivity and competitiveness.

The properties proposed by M. Valcárel and A. Rios should be thought of as a way to hierarchically introduce analytical chemistry. Each group represents a significant part of analytical chemistry and should be dealt with thoroughly by the teacher in order to facilitate a correct understanding by the individual student. The individual groups thus represent the framework by which we can introduce the student to analytical chemistry and rightfully cover the curriculum. It also reflects contradictory relationships in analytical chemistry and proposes some interesting aspects concerning competitiveness, expeditiousness and sensitivity in the laboratory. In industrial context the properties illustrate the paradox observed then assessing various pharmaceutical projects and they are an excellent way to graphically present various dilemmas in drug development.

Analytical techniques in drug design and discovery

Current initiatives in analytical chemistry propose some interesting aspects by combining various division of science towards high yield quality data. Some of these methods are successfully implemented in various phases of drug development and aid in shortening the timeline from lead compound to marketed drug. A collection of these methods are presented below and they should present the reader with a quick overview on some industrially applied analytical techniques. These methods equally show promising results towards scientific advances in analytical chemistry and they demonstrate the implementation of “lean” strategic guidelines in modern drug development and discovery.

“Development of a Ubiquitin Transfer Assay for High Throughput Screening by Fluorescence Resonance Energy Transfer” (3).

Boiscalir et. al (3) propose a new assay based on fluorescence resonance energy transfer (FRET) which successfully could lead to high throughput real time screening of the ubiquitination process in vitro. They furthermore challenge the novel DELFIA assay and suggest that the FRET assay shows lower data variability and due the simplicity of the FRET analysis, the tedious washing, binding and incubation steps in DELFIA are avoided.

Protein degradation by means of ubiquitination involves three enzymatic steps (E1 to E3). Each of these enzymes contributes to the ubiquitination process which leads to the covalent attachment of ubiquitin with ?-aminoacid lysine residues on the target protein (6). The binding of ubiquitin targets the protein for degradation by the proteasomes.

The suggested assay measures the transfer of ubiquitin between the E2 enzyme (Ubc4) and Rsc (human HECT protein). By coupling the Rsc protein to glutathione-S-transferase (GST) and using an anti-GST antibody labelled with Eu3+ it is possible to pre-label the Rsc-GST fusion protein.

The assay exploits the fact that the upon excitation of the compounds, the flourophores Eu3+ and APC exhibits energy transfer and the emission experienced is directly measurable at 665 nm (APC) and 615 nm (Eu3+). To introduce the APC flourophore, the authors have created an ubiquitin-biotin-Streptavidin-Apc complex. Eu3+ acts as the energy donor while APC acts as the energy acceptor, when these are in close proximity (less then 100 Å) to one another, emission is observed from Eu3+ at 615 nm and at 665 nm with APC. The signal intensity presents a means to quantify the ubiquitination process real-time.

The results presented in the paper and the sophisticated experimental set-up revels promising real time data acquisition of biological processes and the method could become a valuable tool in either lead optimization or could successfully be implemented in future HTS assays.

“Drug screening of pharmaceutical discovery compounds by micro-size exclusion chromatography/mass spectrometry” (4).

Paul A. Wabnits and Joseph A. Loo propose a new method which successfully could improve the screening of active ligands in molecular binding studies. Micro-size exclusion chromatography offers a fast and simple way to separate the free ligand from the bound protein-ligand complex. Coupled with liquid chromatography and mass spectrometry the authors present a quick and efficient assay which potentially could lead to high throughput molecular binding quantification.

The metalloenzyme peptide deformylase (PDF) was chosen as the target protein, but in order to achieve sufficient spectroscopic data, the authors exchanged the native Fe2+ with the spectroscopically active Co2+. The binding assay was performed on PDF with several suspected inhibitory drugs (the complete structure was only revealed for actinonin due to commercial reasons).

Various ligands were incubated with PDF, and by means of micro-size exclusion chromatography and mass spectrometry, it was possible to obtain mass spectrums revealing the presence or absence of free ligands. The presence of free ligand should indicate weak/no binding and by performing this with various combinations of drugs the researchers where able to establish the binding rank order of the drugs ((4) table 3).

These data suggest the rank by which various drugs show inhibition of the PDF enzyme, and furthermore introduces a method which could yield fast screening of therapeutic leads towards potential macromolecular targets. The procedure shows high sensitivity and enables researcher to perform fast efficient binding studies of various protein and ligand combinations.

The proposed micro-size exclusion principle is furthermore a great example of the simplicity observed in recent advances in drug development and discovery.

“In vitro identification using fast gradient high performance liquid chromatography combined with tandem mass spectrometry” (5).

In order to perform quick efficient separation of novel drugs and their metabolites, a growing need for optimization of already established analytical techniques is required. A reduction in the time by which researchers can assess potential drugs and their metabolites could be proven valuable in the lead optimization stage of drug design. Even a small reduction in the identification time is of great interest economically and professionally, and could lead to an enhancement in this important phase of drug design.

Coupling fast gradient high liquid chromatography with tandem mass spectrometry could reduce the bottleneck observed in the lead optimization stage as proposed by Cornelis et. al.

The authors present a fast and efficient way to separate and identify isomeric drug metabolites as well as the parent compound, by use of already established analytical processes. Microsomal incubation of the novel drugs produces the suspected metabolites which by means of fast gradient high liquid chromatography are successfully separated. The separation process is proven by coupling the chromatographic process with tandem mass spectrometry. This enables the researcher to establish the presence or absence of various metabolites and indicates the metabolic fate of the investigated drug.

By reducing analysis time researchers could reduce this step and Cornelis et. al propose a technique which successfully could separate metabolites from parent compound in less than 2 minutes. Optimal conditions were obtained upon increasing the flow rate to 2000 µL/min, and enabled successful chromatographic separation of the metabolites and the pure compound ((6) fig. 2+3).

The method is thus of industrial significance due to the time reduction observed in the process and the relatively easy experimental set-up.

Lead discovery and optimization

High throughput screening (HTS)

Industrial high throughput screening (HTS) presents a multidisciplinary science protruding various scientific fields of study. HTS has become a standard in modern drug development signified by a new paradigm shift toward automatization in the lead discovery phase. It is no longer unusual, that pharmaceutical companies have huge screening libraries containing between 500.000 and 1.000.000 compounds (8), controlled by robotics and computational devices. These libraries provide an extensive database containing valuable compound information which linked to recombinant “humanized” in vitro tests could improve expeditiousness and thus as a consequence improve the drug development and discovery process. The libraries should however not be perceived as a clear cut improvement in the lead discovery phase. The expeditiousness of a lead finding is highly dependent on the development of independent assays modelled towards the suspected target. This could potentially produce a bottleneck in discovery phase and should thoroughly be debated in project decision making.

Criteria’s in HTS

The dawn of these enormous screening libraries has sequestered a demand for assays which are able to successfully screen thousands of compounds and furthermore provide sustainable data fast and efficient. This has forced researchers to optimize existing analytical techniques and implement various branches of natural science towards the creation of assays which fulfil specific standards.

The ideal HTS assay should exhibit the following properties (8):

High signal to background ratio (S/B) or signal to noise (S/N) High z´-factor (9) (values >0,5 represent a good assay) Fast screening time Low coefficient of variation (CV %) Large Stokes Shift

These properties are quantifiable measures aiding the researcher in producing high quality HTS assays modelled towards the proposed target. These criteria thus impose boundaries and guidelines which if followed properly optimistically results in ideal screening methods for future implementation in the drug development phases. Even the smallest improvement in one of the parameters could result in higher expeditiousness and potentially a shortening of the individual developmental phases.

As stated above, efficient screening of compounds is essential in locating the perfect lead candidate for future studies. Observing the parameters, it is evident that there are colliding interests between various aspects of analytical chemistry and economical interests. HTS could be grouped with the above mentioned accessory properties in the nine analytical properties (1,2), reflecting upon the balance between expeditiousness and cost effectiveness in terms of economical profitability. It stands in sharp contrast to the basic properties ensuring high precision, sensitivity and selectivity.

There is a fine balance between producing high throughput data and obtaining the adequate precision needed to produce quality results which live up to internal/external standards. As a consequence, the decisions we choose in these two groups highly reflect the accuracy and representativeness found in the capital properties and thus the quality of the results. These conflicting properties should be evaluated in the early drug development phases and it is the research and development team’s job in collaboration with the financial team to define internal standards for which they both can agree upon.

Implementation of quantitative techniques in drug development

HTS assays implemented in the early discovery phase are a powerful tool in establishing the lead compounds interaction with a suspected biological target. Once a suitable lead has been found quantitative studies are needed to further elucidate the leads biological and chemical characteristics. Quantitative studies following these screening assays provide direct quantifiable data concerning the leads metabolic, pharmacokinetic and toxicological fate. These studies provide valuable information concerning the leads biological properties, and the data obtained in the quantitative studies informs the researchers about potential problems such as toxicology, absorption, distribution excretion, pharmacodynamics and metabolism. Quantitative studies are thus often observed in lead optimization studies where they provide important experimental data.

These studies rely on analytical methods with great precision, expeditiousness, sensitivity and they inherit some of the same criteria as HTS assays (se above). Deviations to the above mentioned criteria’s exist and they include the following:

The need for an adequate internal standard Heightened Precision (of great importance in e.g. toxicological studies) High Selectivity Low matrix interference

When conducting these quantitative studies it is of great importance that the data obtained reflects the precise action of the drug and that the methods inherently refrains from producing false positives. It is obvious that quantification of a seemingly unknown drug is difficult. Purification and the construction of an internal standard is alone a tedious task which requires a great deal of experimental work. Introduction of the lead drug into the lead optimization stage furthermore requires the development of specific modelled analytical techniques which potentially could resolve in a bottleneck in the specific phase.

As stated above there is a clear cut difference between the quantitative studies and the screening methods employed upon implementing assays and procedures in drug design and development. Screening has obvious advantages in the lead discovery phase, and is a strong tool which efficiently and swiftly screens numerous compounds for desired characteristics. The screening assays are however restricted upon relying on a great deal of compound information concerning the proposed target and lead compounds. Structural information concerning pKa, lipphilicity, LogP and LogD is needed to develop an assay that follows the above mentioned success criteria. However, once developed, a successful assay generates valuable data for further use and is imperative when evaluating potential lead candidates in the lead discovery phase.

The quantitative study presented by Cornelis et. al (5) is an excellent example of a procedure which could be deployed in the lead optimization stage of drug development. The metabolic fate of the lead compound can be evaluated and quantification is possible in specific ADME/Tox studies. However, the procedure is dependent on extensive knowledge of the mass and structure of the metabolite or drug compound in order to adequately ascertain that we quantify the correct entity.

In conclusion

The drug development and discovery phases introduce some interesting possibilities for various implantation strategies in respects to scientific collaborations and technological advances. One recent advance in liquid chromatography is the dawn of ultra performance liquid chromatography (UPLC) which shows promising results toward quantitative studies (14). The current trends thus reveal great potential in implementation of these new analytical techniques and future studies may contribute to heightened quality in the lead discovery and optimization phases.

The increased governmental requirements for quantitative ADME/Tox studies has forced pharmaceutical companies to invest enormous amounts of money in order to fulfil requirements suggested by the FDA or other local medicines agencies. This has prolonged the development from lead compound to marketed drug and I suggest that this indeed has faltered a paradigm shift in modern drug development. New biotech companies and scientific entrepreneurs are now faced with tough decisions regarding financial aspects in order to asses the sustainability of a suspected leads and they should rightfully evaluate the various properties presented by M. Valcárel and A. Rios. We are positioned in a technological vacuum where technological advances greatly exceed the introduction of new drugs towards patients and the industrial drug development is faced with exciting challenges for the future which successfully may increase the amount of drugs marketed per year.

References

1. Valcárcel M. A modern definition of analytical chemistry. Trends in Analytical Chemistry. 1997. 16. pp 124-131

2. Varcárcel M and Rios A. Teaching analytical properties. Fresenius Journal of Analytical Chemistry. 1997. 354. 202-205.

3. Michael D. Boisclair, Christopher McClure, Serene Josiah, Susan Glass, Steve Bottomley, Shubi Kamerkar and Ilkka Hemmilä. Development of a Ubiquitin Transfer Assay for High Throughput Screening by Fluorescence Resonance Energy Transfer. Journal of Biomolecular Screening, Vol. 5, 2000, pp. 328.

4. Paul A. Wabnitz and Joseph A. Loo. Drug Screening of pharmaceutical discovery compounds by micro-size exclusion chromatography/mass spectrometry. Rapid communications in mass spectrometry, Vol. 16, 2002, pp. 85-91.

5. Cornelis E. C. A. Hop, Phillip R. Tiller and Leslie Romanyshyn. In vitro metabolite identification using fast gradient high performance liquid chromatography combined with tandem mass spectrometry. Rapid communications in mass spectrometry, Vol. 16, 2002, pp. 212-219.

6. Jeremy M. Berg, John L. Tymoczko, Lubert Stryer. Biochemistry 5th edition. W. H. Freeman and Company.

7. György M. Keser? and Gergely M. Makara. Hit discovery and hit-to-lead approaches. Drug Discovery Today. Volume 5, Issue 7, 1 July 2000, Pages 286-293.

8. H P Rang. Drug Discovery and Development. Churchill Livingstone, Elsevier. 2006.

10. Alfonso Espada, Manuel Molina-Martin, Jeffrey Dage2 and Ming-Shang Kuo. Application of LC/MS and related techniques to high-throughput drug discovery. Drug Discovery Today. Volume 13, issue 9-10, May 2008, Page 417-423.

11. Tufts Center for the Study of Drug Development, Backgrounder: How New Drugs Move Through the Development and Approval Process, Boston: November 2001

12. Windhover’s In Vivo: The Business of Medicine Report, Bain drug economics model, 2003

13. http://www.fda.gov/oc/initiatives/criticalpath/whitepaper.html

14. Samuele Pedraglio, Marco Giulio Rozio, Paola Misiano, Veronica Reali, Giulio Dondio, Chiara Bigogno. New perspectives in bio-analytical techniques for preclinical characterization of a drug candidate: UPLC-MS/MS in vitro metabolism and pharmacokinetic studies. Journal of Pharmaceutical and Biomedical Analysis 44 (2007) 665–673.

Defective Drugs – Better Quality of Life or Lies?

Drugstestproduct — Tue, 29 Jun 2010 17:39:29 +0000

We trust our physicians to prescribe us with only the best medications; ones that will cause little to no ill side effects and help us recover in a timely fashion. However, often due to no fault of our doctors, even FDA approved medications are found to be defective, resulting in personal injury and the wrongful death of its victims.

Defective drugs cause the death of thousands each year and the serious injury of close to half a million. Manufacturers claim to spend large amounts of money to test these drugs, so how do they make it onto the marketplace? The answer is sometimes negligence and sometimes deliberate deception on the part of the behemoth pharmaceutical companies:

· A drug is not thoroughly tested

· Unsuspected side effects occur

· Test results are overlooked

· Test results are concealed

· Important questions are not asked, sometimes deliberately

· Prescribed for the wrong reasons

What Drug Categories Are Defective?

Drugs are designed to aid us in recovery or allow us to lead healthier lives, but there are defective drugs found in every drug category.

· Erectile dysfunction drugs such as Viagra have been found to cause a drop in blood pressure and NAION, which is a loss of vision

· Diet drugs often cause more harm than good in countless ways

· Hormone drugs cause tragic complications such as stroke, blood clots and death

· Anti-depressants such as Paxil have been linked to an increase in suicide and birth defects

· Pain killers like OxyContin are highly addictive and subject to abuse

This is not to say that every drug in every category is defective though. But you should give great consideration to possible risks and unforeseen side effects before taking a new prescription drug that will supposedly better your quality of life.

Recent Drug Recalls

While you are eligible for compensation for past defective drugs, it’s the most recent recalls that should signal an alarm bell if you or a loved one had been prescribed to them.

Some recent drug recalls are:

· Heparin–improper labeling and defective manufacturing procedures led to dozens of injuries and deaths as a result of this blood thinner

· Digitek–insufficient quality control led to pills being released with twice the effective dose of this heart arrhythmia medication

· Trasylol–an anti-hemorrhagic drug, this medication is highly toxic to the liver and may have led to as many as 1000 deaths a month at the height of its popularity

· Vioxx – The biggest recall in recent memory was due to Vioxx. Designed to treat acute and chronic pain, arthritis sufferers raved about its benefits. In the years following its approval in 1999, studies found that Vioxx increased the risk of heart attack and stroke

· Fen-phen – A diet drug also known as Redux or Pondimin, Fen-phen was recalled in 1997 due to an increased risk of developing PPH, which can lead to higher blood pressure and heart failure

· Rezulin – An anti-inflammatory that has been found to cause hepatitis

· Baycol – 52 fatal cases of renal failure have been linked to Baycol, which was used to lower cholesterol

· Phenylpropanolamine – An appetite suppressant that has caused strokes and is used in the manufacturing of methamphetamine

Have You Been The Victim of Defective Drugs?

It’s a tragedy that even with oversight from the FDA that defective prescription drugs still leak through and seriously harm or kill its victims.

Effects of Excessive Alcohol Consumption on Social Environment

Drugstestproduct — Sat, 29 May 2010 21:04:01 +0000

Excessive consumption of alcohol has various effects on social environment. Consuming alcohol in the inappropriate times such as, while driving, or operating machines, or in working hours can lead to accidents, loss of work, and may be even more fatal.

Problems Raised By Alcohol Abuse

There are many consequences of abusing alcoholic beverages on social environment, which varies from one another.

• Alcohol abusers are often in the state of drowsiness. They couldn’t perform any work properly.

• As alcohol addiction disables a person to earn, they couldn’t pay bills or credits timely and couldn’t keep good track record of credit history.

• It causes huge damage in production rate and reputation of an organization due to illness of employees

• Driving under the influence of alcohol substances causes accidents.

• Alcohol consumption leads to more absentism for school and college students.

• There would be much absentism at workplace causing loss of valuable man hours

• Due to alcohol abuse, many school and college students are unable concentrate on their studies, which is drawing them towards poor quality of education.

• Alcohol consumption spoils the abusers career and reputation in the workplace and society.

• Chronic consumption of alcohol causes several health problems such as, obesity, liver disease, infertility and if neglected can lead to death.

In such a way, consumption of alcohol has various consequences that may result to get involved in illicit activities. Apart from the effects on social environment, excessive consumption of alcohol leads to become lazier and disregard their health. It disables to act fast and make good decisions. It impairs to perform accurate tasks as it decreases the capabilities of acting and thinking. Moreover, it causes to be unstable amity, inadequate support in any activity and living alone. Alcohol consumption can results to unemployment and will be restrained in to low-income group, which may push them to commit crimes.

This information gives an idea about the major problems caused by alcohol consumption on social environment. With the awareness of these consequences, there can an increase in health care, welfare, and criminal justice and prominently in job performance and family relationships.

Fake Drugs Can Kill

Drugstestproduct — Wed, 19 May 2010 02:47:53 +0000

Millions of patients worldwide are swallowing pills that are either substandard or fake and this can kill them.

This warning comes from the World Health Organization (WHO) that recently called for an immediate global action against the growing epidemic of fake and substandard medicines that are flooding the market, silently killing millions of unwary consumers in the process.

WHO said this problem is present in all countries, especially those with weak drug regulation control and enforcement. In the United States alone, the Center for Medicines in the Public Interest projects counterfeit drug sales will reach $75 billion in 2010, a 92 percent increase from 2005.

The problem with fake generic drugs is that they often fall short of their brand name counterparts since they lack the proper clinical studies showing their safety and efficacy. In the past, generic products were not required by law to be tested for bioequivalence and therapeutic equivalence, posing a threat to consumers. In the rush to save money, patients often purchased these products without considering whether they worked or not.

“We see this happen often because there are many generic drugs in the market and we’ve heard patients complain that they aren’t benefiting from one generic drug to another,” according to Dr. Ricardo Fernando, a diabetologist and president of the Institute for Studies on Diabetes Foundation.

To determine its bioequivalence, a generic drug is tested for its bioavailability or the rate and extent of the drug that reaches the general circulation from an administered dosage form. Ideally, generic drugs should be bioequivalent and therapeutically equivalent to the branded products before they can be substituted for the latter.

Experts say that while generic drugs may be pharmaceutically equivalent, they aren’t necessarily bioequivalent to brand name or innovator drugs since this can be affected by numerous factors like manufacturing techniques, the raw materials and other ingredients used, patient variations in absorption power, the pH (or acidity) of the gastrointestinal (GI) tract, the user’s age, sex, weight, disease status, and interactions with other substances including drugs and food.

Obesity is a big market for fake drugs since many people are desperate to lose weight whether for health or other reasons. For your protection, buy only from reputable dealers or manufacturers. One popular product you can trust is Phenocal – a safe and natural weight loss supplement that will boost your metabolism, suppress your appetite, increase energy levels, and help you lose unwanted pounds. For ore information, visit http://www.phenocal.com.

The Benefits Of Generic Drugs

Drugstestproduct — Tue, 18 May 2010 13:10:37 +0000

Sometimes vast amounts of time and money expended on research and development of a new drug, exclusive manufacturing patents are given to drug companies for new products. This allows the developing company a chance to be the only source for a new medical treatment for a number of years.

This time will vary. A patent in the United States is usually given for a twenty year period, but since this time begins counting down from the beginning of research, the effective market window can be years less. Once the originating company has had a chance to make back their investment, the patent expires so that other drug companies may also manufacture the drug under a generic label.

These generic drugs are supposedly the exact same chemical compound although a few variations are allowed so long as the counterpart generic can match the same bioequivalent effects of the original compound. Once these copycat drugs come on the market, the competition between them and the original product generally creates a price drop that can save the consumer and insurance companies a great deal of money while providing the same beneficial medicine.

There are two major reasons why generic drugs can be sold for a greatly lowered price than the original patented drugs. Firstly, the research and development stage is already been done so there is no great cost associated with their production. Also, with competition for the drug, regular market practices take over and the ability to choose between brands will usually keep the cost at a competitive level.

To a lesser degree, generic drug producers can also take advantage of the previous advertising by the original company that has familiarized people with the drug and will not have to get the idea of the product before the public view.

Once the exclusive patent expires on a drug there is almost no way to renew it. Patent laws vary from country to country and there are a few that do not recognize and accept the patents from the country of origin. Once a patent has expired it is available for duplication. An originating company cannot extend the patent by changing some of the formula as this is in effect making a new drug, however similar, and would have to go through the entire qualifying process again.

There is also the consideration that while a specific drug formula may be under patent, there can be other forms available provided the active ingredient is not patented. It then falls on the prescribing doctor to know which form of a certain chemical will have the desired effect on his patient.

There are regulatory tests to assure that the generic form of a drug is equivalent to the original although some small changes in the exact chemical elements are allowed provided the substituted ingredients are equally effective as the original. This is usually the case in some of the chemicals that help carry the active ingredient into the blood stream.

While these substitutes are tested to see that they perform equally, there is the bias among some doctors that only the original works the way they want and will disallow generic drugs to be filled by a pharmacy. There is no scientific rationale for this as the generic drugs have to pass the equivalence test before they can be released.