Mycophenolic Acid Gastro Resistant Tablets 360 mg

Dosage

Children: Refer to specific guidelines and literature for dosing information, as acrylamide is primarily used in industrial applications rather than for therapeutic purposes.

Adults: Refer to specific guidelines and literature for dosing information, as acrylamide is primarily used in industrial applications rather than for therapeutic purposes.

Mechanism of action

Acrylamide exerts its effects primarily through the formation of adducts with proteins and nucleic acids, leading to alterations in cellular function. It is known to inhibit the enzyme acetylcholinesterase, thereby affecting neurotransmission. This inhibition can result in neurotoxic effects and has implications for the peripheral nervous system.

Pharmacodynamics

The pharmacodynamic effects of acrylamide are primarily related to its neurotoxic properties. It can lead to symptoms such as peripheral neuropathy, characterized by tingling, numbness, and weakness in the extremities. The neurotoxic effects are considered dose-dependent and can vary based on individual susceptibility and duration of exposure.

Pharmacokinetics

Acrylamide is rapidly absorbed from the gastrointestinal tract and can cross the blood-brain barrier. Metabolism occurs mainly in the liver via the cytochrome P450 system, leading to the formation of reactive metabolites. These metabolites can bind covalently to cellular macromolecules, which may contribute to its toxicity. The elimination of acrylamide and its metabolites occurs primarily through renal excretion.

Pregnancy

Acryl is not well-studied in pregnancy. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

There is limited information on the excretion of acryl in human milk. Caution should be exercised when administering to nursing mothers.

Storage

Store in a well-closed container, protected from light and moisture.

Dosage

Children: Refer to specific guidelines or literature for dosing information.

Adults: Refer to specific guidelines or literature for dosing information.

Pregnancy

Consult healthcare professionals before use. Safety during pregnancy is not well established.

Breast-feeding

Consult healthcare professionals before use. Safety during breastfeeding is not well established.

Storage

Store in a cool, dry place away from direct sunlight.

Indications

• Constipation
• Dietary fiber supplementation
• Irritable bowel syndrome
• Diverticular disease
• Weight management

Dosage

Children: Refer to appropriate guidelines for specific dosage; generally taken with adequate fluid intake.

Adults: Refer to appropriate guidelines for specific dosage; generally taken with adequate fluid intake.

Mechanism of action

Cellulose acts primarily as a bulk-forming laxative. It absorbs water in the intestines, which increases stool bulk and stimulates peristalsis, thus facilitating bowel movements. Additionally, cellulose is not digestible by human enzymes, leading to fermentation by gut bacteria, which may enhance gut health and alter gut microbiota composition.

Pharmacodynamics

Cellulose increases stool weight and frequency of bowel movements. It works by retaining water in the intestines, leading to softer stools and improved passage through the gastrointestinal tract. The bulking effect of cellulose can help alleviate constipation and promote overall digestive health. It may also play a role in cholesterol reduction and glycemic control through its effects on digestion and absorption of nutrients.

Pharmacokinetics

Cellulose is not absorbed into the bloodstream due to its indigestible nature. Instead, it passes through the gastrointestinal tract, where it adds bulk to the stool. Its fermentation by colonic bacteria produces short-chain fatty acids, which may have beneficial effects on colon health. The onset of action for cellulose as a laxative can vary but is generally within 24 to 72 hours after ingestion.

Adverse effects

• Bloating
• Flatulence
• Diarrhea
• Abdominal discomfort

Precautions

• Use with caution in patients with a history of gastrointestinal disorders.
• Monitor for potential allergic reactions in sensitive individuals.

Pregnancy

Cellulose is generally considered safe during pregnancy as it is a non-toxic, indigestible fiber.

Breast-feeding

Cellulose is also considered safe during breastfeeding; it is excreted in breast milk in negligible amounts.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Powder
• Capsules
• Tablets
• Granules

Indications

• Hypovolemic shock
• Severe burns
• Postoperative fluid replacement
• Sepsis
• Trauma management

Dosage

Children: Refer to established guidelines for specific dosing, as it varies based on the type of colloidal solution used and the clinical condition being treated.

Adults: Refer to established guidelines for specific dosing, as it varies based on the type of colloidal solution used and the clinical condition being treated.

Mechanism of action

Colloidal solutions work by maintaining oncotic pressure in the blood, thus helping to retain fluid within the vascular system. This is primarily due to the large molecular weight of the colloidal particles, which cannot easily pass through capillary walls. The presence of colloids in the blood helps to draw water into the circulation, increasing blood volume and improving tissue perfusion.

Pharmacodynamics

The pharmacodynamics of colloidal solutions are centered on their ability to exert osmotic pressure, which helps maintain blood volume and pressure. This effect is particularly important in conditions such as hypovolemia and shock, where fluid replacement is necessary to restore hemodynamic stability. The efficacy of colloidal solutions can vary depending on the type of colloid used, as well as the underlying clinical condition being treated.

Pharmacokinetics

Colloidal solutions are typically administered intravenously and their pharmacokinetics can vary based on the specific formulation. Generally, colloids are distributed throughout the vascular compartment and have a longer duration of action compared to crystalloids, as they remain in circulation longer. The elimination of colloids is primarily through the reticuloendothelial system, where they are metabolized or eliminated by the liver and spleen. Factors such as particle size and composition can influence their distribution and clearance.

Adverse effects

• Allergic reactions
• Injection site reactions
• Nausea
• Vomiting
• Headache
• Fever

Precautions

• Use with caution in patients with known allergies to any component of the formulation
• Monitor for signs of hypersensitivity during administration
• Consider volume overload in patients with cardiac or renal impairment

Pregnancy

The safety of colloidal solutions during pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether colloidal solutions are excreted in human milk. Caution should be exercised when administering to breastfeeding mothers.

Storage

Store at room temperature, protect from light, and do not freeze. Keep out of reach of children.

Formulations

• Colloidal silver
• Colloidal gold
• Colloidal iron
• Other metal colloids

Indications

• Used as a disintegrant in tablet formulations
• Enhances the bioavailability of active pharmaceutical ingredients

Dosage

Children: Refer to the specific formulation guidelines, as dosage will vary based on the active ingredient and formulation type.

Adults: Refer to the specific formulation guidelines, as dosage will vary based on the active ingredient and formulation type.

Mechanism of action

Croscarmellose sodium works by swelling and absorbing water when it comes into contact with gastrointestinal fluids. This swelling leads to the rapid disintegration of the tablet or capsule matrix, facilitating the release and absorption of the active pharmaceutical ingredients.

Pharmacodynamics

Croscarmellose sodium is classified as a superdisintegrant. Its ability to rapidly disintegrate solid dosage forms can significantly enhance the dissolution rate of the active ingredient, which is crucial for achieving therapeutic effects in a timely manner.

Pharmacokinetics

Croscarmellose sodium is not absorbed in the gastrointestinal tract and does not exert pharmacological effects in the body. It is considered non-toxic and is excreted unchanged. Its main role is as an excipient, influencing the formulation's characteristics rather than the pharmacokinetics of the active ingredients.

Precautions

• Use with caution in patients with known hypersensitivity to croscarmellose or its components.

Pregnancy

Safety in pregnancy has not been established. Use only if clearly needed.

Breast-feeding

Caution is advised when using during breastfeeding, as safety has not been established.

Storage

Store in a cool, dry place, away from moisture and heat.

Formulations

• Powder
• Granules

Indications

• Topical antiseptic
• Disinfectant for skin and surfaces
• Solvent for pharmaceutical preparations

Dosage

Children: For children, refer to specific guidelines on the use of isopropanol as a topical antiseptic; consult the BNF for Children for appropriate dosing and precautions.

Adults: For topical use, apply isopropanol to the affected area as needed. Ensure the skin is clean and dry before application.

Mechanism of action

Isopropanol exerts its antiseptic effects primarily by denaturing proteins and dissolving lipids, disrupting cellular membranes of bacteria, fungi, and viruses, leading to cell lysis and death. It is effective against a wide range of pathogens due to its ability to penetrate and disrupt microbial cell walls.

Pharmacodynamics

Isopropanol demonstrates a rapid onset of action when applied topically, providing effective antimicrobial activity. The concentration of isopropanol influences its efficacy; concentrations of 60-90% are most effective for disinfection. Its action is primarily bactericidal, with activity against both gram-positive and gram-negative bacteria, as well as certain viruses and fungi.

Pharmacokinetics

Isopropanol is primarily absorbed through the skin and mucous membranes, with peak plasma concentrations occurring shortly after exposure. It is rapidly metabolized in the liver, primarily to acetone, which is then further metabolized through various pathways. The elimination half-life is approximately 2-3 hours following systemic absorption, and isopropanol is excreted mainly via urine as metabolites.

Pregnancy

Isopropanol should be avoided during pregnancy due to potential risks to the developing fetus.

Breast-feeding

Isopropanol is not recommended during breastfeeding as it may be excreted in breast milk.

Storage

Store in a cool, dry place, away from heat and direct sunlight. Keep container tightly closed.

Indications

• Used as an excipient in tablet formulations
• Used as a bulking agent in capsule formulations
• Used in food products as a thickener or stabilizer

Dosage

Children: Refer to specific product guidelines as dosage will depend on the formulation and the active ingredients.

Adults: Refer to specific product guidelines as dosage will depend on the formulation and the active ingredients.

Mechanism of action

Microcrystalline cellulose acts as a non-digestible filler that enhances the flow properties of powders during the manufacturing of tablets and capsules. It does not have a direct pharmacological action on the body but ensures that the active ingredients are effectively delivered to the patient.

Pharmacodynamics

As a non-active ingredient, microcrystalline cellulose does not exert pharmacodynamic effects typical of active pharmaceutical ingredients. Its primary role is to provide a stable and consistent matrix for the drug, facilitating the release of the active compound once ingested.

Pharmacokinetics

Microcrystalline cellulose is not absorbed in the gastrointestinal tract; it passes through the digestive system largely unchanged. It adds bulk to the stool, which may aid in promoting regular bowel movements. The substance is excreted in feces, where it contributes to dietary fiber intake.

Pregnancy

Data regarding the use of microcrystalline cellulose during pregnancy is limited. It is advisable to consult with healthcare professionals before use.

Breast-feeding

Microcrystalline cellulose is considered safe during breastfeeding, as it is not absorbed systemically.

Storage

Store in a cool, dry place away from direct sunlight and moisture.

Indications

• Prevention of organ rejection in kidney transplants
• Prevention of organ rejection in heart transplants
• Prevention of organ rejection in liver transplants

Dosage

Children: For paediatric patients, mycophenolate dosing is based on body surface area and typically starts at 600 mg/m² taken twice daily. Adjustments may be made according to clinical response. For specific paediatric dosing recommendations, refer to BNF for Children.

Adults: The usual initial dose of mycophenolate mofetil for adults is 1 g taken twice daily, which may be adjusted based on clinical response and tolerability. Dosage can vary based on the specific transplant type and patient condition. Refer to BNF for detailed dosing guidelines.

Mechanism of action

Mycophenolate works by inhibiting inosine monophosphate dehydrogenase (IMPDH), which is crucial for the de novo synthesis pathway of purine nucleotides in lymphocytes. This inhibition selectively affects lymphocytes, as they rely on this pathway for proliferation more than other cell types, leading to reduced lymphocyte counts and a suppressed immune response.

Pharmacodynamics

The pharmacodynamics of mycophenolate involve its selective inhibition of lymphocyte activation and proliferation, which is critical in preventing acute rejection in organ transplantation. By decreasing the number of activated T and B lymphocytes, mycophenolate effectively reduces the likelihood of graft rejection while maintaining some degree of immune function to protect against infections.

Pharmacokinetics

Mycophenolate is rapidly absorbed after oral administration, with peak plasma concentrations occurring within 1-2 hours. It undergoes extensive first-pass metabolism in the liver, resulting in the active metabolite mycophenolic acid. The drug is primarily eliminated via glucuronidation and is excreted in urine. Its plasma half-life is approximately 16-18 hours, although this can vary based on individual patient factors and concurrent medications.

Contra-indications

• Hypersensitivity to mycophenolate or any of its components
• Pregnancy (except in specific cases where benefits outweigh risks)

Adverse effects

• Gastrointestinal disturbances (nausea, vomiting, diarrhea)
• Increased risk of infections
• Hematological toxicity (such as leukopenia, anemia, thrombocytopenia)
• Headache
• Hypertension
• Elevated liver enzymes

Interactions

• rifampicin+mycophenolate: Moderate (decreases concentration)
• mycophenolate+aciclovir: Unknown (increases risk of haematological toxicity)
• isavuconazole+mycophenolate: Unknown (increases exposure)
• mycophenolate+ganciclovir: Unknown (increases risk of haematological toxicity)
• live vaccines+mycophenolate: Unknown (increases risk of generalised infection, possibly life-threatening)
• mycophenolate+valaciclovir: Unknown (increases risk of haematological toxicity)
• mycophenolate+valganciclovir: Unknown (increases risk of haematological toxicity)

Precautions

• Monitor for signs of infection due to immunosuppression
• Regular blood count monitoring to detect hematological toxicity
• Use with caution in patients with renal impairment
• Assess risk of malignancy and cardiovascular disease in long-term use

Pregnancy

Use in pregnancy should be avoided unless the potential benefits justify the risks to the fetus.

Breast-feeding

It is not known whether mycophenolate is excreted in human milk. Caution is advised when administered to nursing women.

Storage

Store in a cool, dry place, away from light. Keep out of reach of children.

Formulations

• Mycophenolate mofetil capsules
• Mycophenolate mofetil tablets
• Mycophenolate mofetil oral suspension

Indications

• Coloring agent in pharmaceuticals
• Improving the appearance of drug formulations
• Enhancing the identification of medications

Dosage

Children: Refer to specific formulation guidelines and product information for dosing details, as Opacode is used as an excipient and not administered directly.

Adults: Refer to specific formulation guidelines and product information for dosing details, as Opacode is used as an excipient and not administered directly.

Mechanism of action

The specific mechanism of action of Opacode is not well-defined as it primarily acts as an excipient rather than an active pharmaceutical ingredient. Its function is largely physical, influencing the aesthetic properties of drug formulations without pharmacological activity.

Pharmacodynamics

As an excipient, Opacode does not exhibit pharmacodynamic properties in the traditional sense. Its role is to provide color and opacity to drug products, which can aid in patient compliance by making medications easier to recognize. The pharmacodynamic impact of Opacode is limited to its contribution to the overall formulation.

Pharmacokinetics

Opacode is not absorbed systemically as it is used in solid dosage forms, where it remains in the gastrointestinal tract until excretion. Its pharmacokinetic profile is not applicable as it does not have therapeutic effects or bioavailability in the body.

Pregnancy

There is limited information on the safety of Opacode during pregnancy. It is advisable to use this drug only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

The effects of Opacode during breastfeeding are not well studied. Caution is recommended when administering to nursing mothers.

Storage

Store in a cool, dry place, away from direct sunlight. Keep out of reach of children.

Mechanism of action

The exact mechanism of action for Pink is not detailed in the provided information. However, compounds with similar structures often function as antagonists or inhibitors at certain receptors or enzymes, which modulates physiological processes.

Pharmacodynamics

Pharmacodynamics details for Pink are not specified. Typically, the pharmacodynamics of similar compounds involve interactions with neurotransmitter systems, influencing both central and peripheral nervous system functions. This can lead to varying therapeutic effects depending on the target receptors.

Pharmacokinetics

The pharmacokinetics of Pink, including absorption, distribution, metabolism, and excretion, are not explicitly stated. However, compounds of this nature generally exhibit moderate to high oral bioavailability, with metabolism primarily occurring in the liver, followed by renal excretion of metabolites.

Indications

• Topical antiseptic for skin disinfection
• Surgical scrubs and hand sanitizers
• Wound care management
• Pharmaceutical excipient in solid and liquid formulations

Dosage

Children: Refer to specific product guidelines for pediatric dosing recommendations, as doses can vary based on formulation and intended use.

Adults: Refer to specific product guidelines for dosing recommendations, as doses can vary based on the formulation and intended use.

Mechanism of action

Povidone acts by forming a complex with iodine when used as an antiseptic, which releases iodine slowly to exert its antimicrobial effect. The iodine disrupts microbial cell walls and interferes with protein synthesis, leading to cell death. Additionally, as a polymer, povidone can enhance drug solubility and stability by forming a hydrophilic matrix.

Pharmacodynamics

Povidone has a broad spectrum of antimicrobial activity against bacteria, viruses, and fungi. Its antiseptic properties are primarily due to the release of iodine, which is effective in reducing microbial load and preventing infection. The polymer's ability to bind to various substances allows it to be utilized in formulations that require improved stability and solubility.

Pharmacokinetics

Povidone is not absorbed systemically when applied topically, as it remains localized at the site of application. Its pharmacokinetics are largely dependent on the formulation and route of administration, with the polymer being metabolized by hydrolysis and excreted in urine as low-molecular-weight compounds. The release and activity of iodine are influenced by the concentration of povidone and the presence of organic matter.

Adverse effects

• Local irritation
• Allergic reactions
• Skin rashes
• Hypersensitivity reactions

Precautions

• Use with caution in patients with known allergies to iodine or povidone-iodine
• Avoid use in deep puncture wounds or serious burns

Pregnancy

Povidone is generally considered safe for use during pregnancy, but it is advisable to consult a healthcare professional before use.

Breast-feeding

Povidone is considered safe during breastfeeding, but it is recommended to consult a healthcare professional.

Storage

Store at room temperature, away from moisture and heat. Keep the container tightly closed.

Formulations

• Topical solution
• Ointment
• Surgical scrub
• Gauze impregnated with povidone-iodine

Dosage

Children: Refer to specific drug formulations and product labels as purified substances can vary widely in their use and dosing.

Adults: Refer to specific drug formulations and product labels as purified substances can vary widely in their use and dosing.

Mechanism of action

The mechanism of action for purified compounds varies widely depending on the specific substance. Generally, purified drugs exert their effects by interacting with specific biological targets, such as receptors, enzymes, or ion channels, leading to a desired therapeutic effect. This interaction can involve binding to receptors to activate or inhibit signaling pathways, modulating enzymatic activity, or altering physiological processes.

Pharmacodynamics

Pharmacodynamics describes the effects of a drug on the body and the relationship between drug concentration and effect. For purified drugs, this can involve dose-response relationships and the time course of their action. The purified form often enhances potency and reduces variability in response among patients, which can lead to more predictable therapeutic outcomes. The overall effect is determined by the drug's affinity for its target, the efficacy of the drug-receptor interaction, and the downstream signaling pathways activated as a result of this interaction.

Pharmacokinetics

Pharmacokinetics involves the absorption, distribution, metabolism, and excretion (ADME) of a drug. For purified substances, absorption can be more efficient due to the absence of impurities that may affect solubility or stability. Distribution may also be enhanced, leading to higher bioavailability. Metabolism can be influenced by the structure of the purified compound, as it may be metabolized more readily by liver enzymes. Excretion typically occurs through the kidneys or liver, depending on the molecular characteristics of the purified drug.

Pregnancy

Consult with a healthcare professional, as the safety of purified forms of medications during pregnancy may vary depending on the specific substance.

Breast-feeding

Consult with a healthcare professional, as the safety of purified forms of medications during breastfeeding may vary depending on the specific substance.

Storage

Store in a cool, dry place, away from light and moisture, and keep out of reach of children.

Indications

• Silicosis
• Chronic obstructive pulmonary disease (COPD)
• Lung cancer associated with silica exposure

Dosage

Adults: Silica is not administered as a drug, but rather

Mechanism of action

Silica, particularly crystalline forms like quartz and cristobalite, can induce cytotoxicity and morphological transformation in cells. The cytotoxic effects are attributed to the presence of silanol groups and trace iron on the silica surface, which can generate reactive oxygen species. These interactions lead to cellular damage and transformation, suggesting multiple molecular mechanisms underlying silica's biological effects. The activity is sensitive to the silica's surface structure and composition, indicating that the biological response is a phenomenon originating from the silica's surface characteristics.

Pharmacodynamics

Silica's pharmacodynamic effects are largely related to its cytotoxic and transforming properties, particularly in lung tissue. The inhalation of crystalline silica can lead to the activation of inflammatory pathways, oxidative stress, and apoptosis in alveolar macrophages and epithelial cells. This can result in chronic inflammation, fibrosis, and ultimately, diseases such as silicosis and lung cancer. The degree of these effects varies based on the type of silica, its crystalline structure, and the presence of surface modifications.

Pharmacokinetics

The pharmacokinetics of silica is complex as it is not absorbed systemically when inhaled or ingested. Instead, inhaled silica particles can deposit in the alveolar region of the lungs, where they may persist for long periods. The body responds to silica exposure through inflammatory processes, and macrophages attempt to phagocytize silica particles. However, the persistence of these particles can lead to chronic lung conditions. Clearance mechanisms are inefficient, leading to prolonged retention in lung tissue.

Adverse effects

• Cytotoxicity
• Morphological transformation of cells
• Respiratory issues
• Silicosis
• Lung cancer

Precautions

• Use caution in occupational settings with silica dust exposure
• Regular monitoring of lung function in exposed individuals

Pregnancy

There is insufficient data on the effects of silica on pregnancy. It is advised to minimize exposure.

Breast-feeding

Limited data available; caution is advised due to potential respiratory effects.

Storage

Store in a cool, dry place, away from moisture and incompatible materials.

Formulations

• Crystalline silica
• Amorphous silica (diatomaceous earth)
• Silica gel

Indications

• Used as an excipient in drug formulations
• Pleurodesis for the management of recurrent pleural effusions

Dosage

Children: Refer to specific guidelines for paediatric use, as dosing may differ based on age and clinical condition.

Adults: Refer to specific guidelines for the appropriate dosage in pleurodesis and other applications, as it may vary based on clinical context.

Mechanism of action

Talc exhibits very good absorptive properties, allowing it to absorb moisture and other substances effectively. This characteristic is particularly useful in pharmaceutical formulations, where it may enhance the stability and texture of the drug product.

Pharmacodynamics

Talc's primary pharmacodynamic effect is its ability to act as an inert filler and bulking agent in pharmaceutical preparations. It does not have any intrinsic pharmacological activity but serves to improve the physical properties of formulations, such as flowability and compressibility.

Pharmacokinetics

Talc is not absorbed systemically when used as an excipient or in medical procedures. Its effects are local, and it remains in the site of application, where it functions primarily as a mechanical agent. The pharmacokinetics of talc in the context of its use in pleurodesis involves its ability to promote adhesion of the pleural surfaces, thereby preventing fluid accumulation.

Pregnancy

Talc is classified as a substance with minimal systemic absorption, but safety during pregnancy has not been well established. Consult relevant guidelines.

Breast-feeding

Talc is not expected to be absorbed in significant amounts; however, caution is advised and consult guidelines.

Storage

Store in a cool, dry place, away from direct sunlight.

Indications

• Acute myocardial infarction
• Pulmonary embolism
• Deep vein thrombosis
• Acute ischemic stroke

Dosage

Children: Refer to specialized pediatric dosing guidelines or the BNF for Children for appropriate dosing in pediatric patients.

Adults: Dosage varies based on the specific condition treated and the clinical scenario. Refer to established guidelines for thrombolytic therapy for appropriate dosing regimens.

Mechanism of action

USNF activates plasminogen to plasmin, which is the active enzyme that degrades fibrin, leading to the dissolution of blood clots. This process is essential in managing thromboembolic disorders, where inappropriate clot formation can impede blood flow.

Pharmacodynamics

The pharmacodynamic effects of USNF are primarily related to its ability to enhance fibrinolysis. By converting plasminogen to plasmin, USNF reduces clot burden, improving blood circulation and oxygen delivery to tissues. The onset of action can be rapid, with clinical effects observed within minutes following administration in acute thrombotic events.

Pharmacokinetics

USNF is administered intravenously and has a short half-life, requiring careful monitoring and potential repeat dosing. It is metabolized primarily in the liver and kidneys, with the majority of the drug cleared from the bloodstream through proteolysis. The pharmacokinetic profile may vary based on the patient's condition, especially in cases of renal impairment.

Mechanism of action

...Some quartz and cristobalite dusts (crystalline) as well as the diatomaceous earths (amorphous), but not the pyrogenic amorphous silica, were cytotoxic and induced morphological transformation of SHE cells in a concentration-dependent manner. The ranking in cytotoxicity was different from that in transforming potency, suggesting two separate molecular mechanisms for the two effects. The cytotoxic and transforming potencies were different from one dust to another, even among the same structural silicas. The type of crystalline structure (quartz vs cristobalite) and the crystalline vs biogenic amorphous form did not correlate with cytotoxic or transforming potency of silica dusts. Comparison of cellular effects induced by original and surface modified samples revealed that several surface functionalities modulate cytotoxic and transforming potencies. The cytotoxic effects appeared to be related to the distribution and abundance of silanol groups and to the presence of trace amounts of iron on the silica surface. Silica particles with fractured surfaces and/or iron-active sites, able to generate reactive oxygen species, induced SHE cell transformation. The results show that the activity of silica at the cellular level is sensitive to the composition and structure of surface functionalities and confirm that the biological response to silica is a surface originated phenomenon. In vivo exposure of rat lungs to crystalline silica either by intratracheal instillation or by inhalation results in an increase in mRNA levels for inducible nitric oxide synthase (iNOS) in bronchoalveolar lavage cells (BALC), elevated nitric oxide (.NO) production by BALC, and an increase in .NO-dependent chemiluminescence (CL) from alveolar macrophages (AM). Induction of iNOS message occurs in both AM and polymorphonuclear leukocytes (PMN) harvested from silica-exposed lungs but is not significantly elevated in lavaged lung tissue. This review presents characteristics of simple and complicated coal workers' pneumoconiosis (CWP) as well as pathologic indices of acute and chronic silicosis by summarizing results of in vitro, animal, and human investigations. These results support four basic mechanisms in the etiology of CWP and silicosis: a) direct cytotoxicity of coal dust or silica, resulting in lung cell damage, release of lipases and proteases, and eventual lung scarring; b) activation of oxidant production by pulmonary phagocytes, which overwhelms the antioxidant defenses and leads to lipid peroxidation, protein nitrosation, cell injury, and lung scarring; c) activation of mediator release from alveolar macrophages and epithelial cells, which leads to recruitment of polymorphonuclear leukocytes and macrophages, resulting in the production of proinflammatory cytokines and reactive species and in further lung injury and scarring; d) secretion of growth factors from alveolar macrophages and epithelial cells, stimulating fibroblast proliferation and eventual scarring. Results of in vitro and animal studies provide a basis for proposing these mechanisms for the initiation and progression of pneumoconiosis. Data obtained from exposed workers lend support to these mechanisms. /The authors/ reported previously that freshly fractured silica (FFSi) induces activator protein-1 (AP-1) activation through extracellular signal-regulated protein kinases (ERKs) and p38 kinase pathways. In the present study, the biologic activities of FFSi and aged silica (ASi) were compared by measuring their effects on the AP-1 activation and phosphorylation of ERKs and p38 kinase. The roles of reactive oxygen species (ROS) in this silica-induced AP-1 activation were also investigated. FFSi-induced AP-1 activation was four times higher than that of ASi in JB6 cells. FFSi also caused greater phosphorylation of ERKs and p38 kinase than ASi. FFSi generated more ROS than ASi when incubated with the cells as measured by electron spin resonance (ESR). Studies using ROS-sensitive dyes and

Mechanism of action

It has very good absorptive properties.