LACTIV (VAGINAL WASH)

Indications

• Homocystinuria
• Type I Gaucher's disease (specialist use only)

Dosage

Children: Refer to BNF for Children for specific dosing guidelines.

Adults: Refer to BNF for specific dosing guidelines.

Mechanism of action

Betaine acts as a methyl donor in the transsulfuration pathway, facilitating the conversion of homocysteine to methionine and thereby reducing homocysteine levels.

Pharmacodynamics

Betaine reduces plasma homocysteine concentrations, which is beneficial in conditions such as homocystinuria. It also has a role in osmoregulation and may influence cellular metabolism.

Pharmacokinetics

Betaine is well absorbed after oral administration, with a bioavailability of approximately 90%. It is primarily excreted in the urine as betaine and its metabolites.

Adverse effects

• abdominal discomfort
• agitation
• alopecia
• appetite decreased
• brain oedema
• diarrhoea
• glossitis
• irritability
• nausea
• skin reactions
• urinary incontinence
• vomiting
• arthralgia
• asthenia
• chest discomfort
• dizziness
• dyspnoea
• fever
• flushing
• gastrointestinal discomfort
• headache
• hypersensitivity
• hypertension
• hypotension
• infusion-related reactions
• nausea
• pain
• skin reactions
• tachycardia

Interactions

• may be given with supplements of Vitamin B12, pyridoxine, and folate under specialist advice

Precautions

• use in conjunction with dietary restrictions
• monitor plasma-methionine concentration before and during treatment
• interrupt treatment if symptoms of cerebral oedema occur
• use with caution in pregnancy due to limited information
• use with caution in breastfeeding due to lack of information

Pregnancy

Manufacturer advises avoid unless essential-limited information available.

Breast-feeding

Manufacturer advises caution-no information available.

Storage

Store in a cool, dry place; protect from light.

Formulations

• Cystadane oral powder 1 gram per 1 gram

Indications

• Cleansing agent in shampoos
• Emulsifier in lotions and creams
• Foam booster in body washes
• Thickening agent in personal care products

Dosage

Children: Refer to specific product guidelines, as doses vary by formulation and intended use.

Adults: Refer to specific product guidelines, as doses vary by formulation and intended use.

Mechanism of action

Cocamidopropyl functions by reducing the surface tension of water, allowing for better spreading and penetration in formulations. It interacts with skin and hair, facilitating the removal of dirt and oil. Its amphiphilic properties enable it to stabilize emulsions and enhance foaming capabilities, contributing to the overall sensory experience of products.

Pharmacodynamics

Due to its surfactant properties, cocamidopropyl provides cleansing effects by solubilizing oils and dirt on the skin and hair. It creates micelles that trap impurities, which are then easily washed away. Its mildness is attributed to the coconut-derived origin, which is less irritating compared to synthetic surfactants. This makes it suitable for frequent use without significant disruption to the skin barrier.

Pharmacokinetics

Cocamidopropyl is primarily used topically, and its absorption through the skin is minimal. It is not systemically bioactive when applied as intended in personal care products. The compound is generally considered safe, with low toxicity profiles reported in clinical studies. Its effects are localized to the application site, and it is not expected to accumulate in systemic circulation.

Adverse effects

• Allergic reactions
• Skin irritation
• Eye irritation
• Respiratory issues in sensitized individuals

Precautions

• Use with caution in individuals with known sensitivities or allergies to surfactants
• Conduct a patch test before widespread use on skin

Pregnancy

There is limited data on the safety of cocamidopropyl in pregnancy; use with caution and only if clearly needed.

Breast-feeding

Limited data available; consult a healthcare provider before use.

Storage

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

Formulations

• Cocamidopropyl betaine in shampoos and conditioners
• Cocamidopropyl hydroxysultaine in cleansing products

Indications

• Topical treatment of skin wounds
• Moisturizing dry skin
• Management of minor burns
• Soothing irritations and inflammation of the skin

Dosage

Children: Refer to the BNF for Children for specific dosing

Adults: Apply to the affected area as needed, following the specific product instructions.

Mechanism of action

Dexpanthenol is enzymatically converted to pantothenic acid, which is integral to the formation of coenzyme A. This coenzyme acts as a cofactor in numerous enzymatic reactions, particularly those related to protein metabolism in epithelial tissues. The topical application of dexpanthenol promotes fibroblast proliferation and accelerates wound healing through enhanced re-epithelialization. It also increases the availability of coenzyme A for acetylcholine synthesis, which can enhance intestinal motility by improving peristalsis.

Pharmacodynamics

Dexpanthenol, through its conversion to pantothenic acid, plays a vital role in the synthesis of coenzyme A, which is necessary for various metabolic processes, including the transfer of acetyl groups. It directly influences the production of acetylcholine, the neurotransmitter responsible for parasympathetic nervous system functions, which include maintaining normal intestinal activity. A deficiency in acetylcholine can lead to reduced peristalsis and conditions such as adynamic ileus.

Pharmacokinetics

Dexpanthenol is well absorbed when applied topically. It penetrates the skin effectively, reaching the underlying tissues where it can exert its biological effects. The metabolism of dexpanthenol involves its conversion to pantothenic acid, which further participates in the synthesis of coenzyme A. The elimination half-life and extent of systemic absorption vary based on the formulation and route of administration, but topical use typically results in low systemic exposure.

Adverse effects

• Skin irritation
• Allergic reactions

Precautions

• Use with caution in patients with known allergies to dexpanthenol or related compounds.

Pregnancy

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

Breast-feeding

Dexpanthenol is considered safe during breastfeeding, but consult a healthcare provider for specific recommendations.

Storage

Store at room temperature, away from light and moisture. Keep out of reach of children.

Formulations

• Topical cream
• Topical ointment
• Topical solution

Indications

• Nutritional support
• Prevention of chronic diseases
• Support for digestive health
• Antioxidant support
• Hydration

Dosage

Children: In children, the recommendation for fruit intake varies by age, with guidelines typically suggesting 1 to 2 servings per day, depending on age and dietary requirements.

Adults: Fruits are generally consumed as part of a balanced diet, with recommendations often suggesting 5 portions of fruits and vegetables per day, though specific amounts may vary based on individual dietary needs.

Mechanism of action

Fruits contain various bioactive compounds, including vitamins (such as vitamin C and folate), minerals (like potassium), dietary fiber, and phytochemicals (such as flavonoids and carotenoids). These components contribute to their health benefits through various mechanisms, including antioxidant activity, modulation of inflammation, and enhancement of immune function.

Pharmacodynamics

The pharmacodynamic effects of fruits are largely attributed to their phytochemical content, which can influence metabolic pathways, reduce oxidative stress, and improve cardiovascular health. The fiber content aids in digestion and can contribute to maintaining healthy cholesterol levels. The vitamins and minerals support various physiological functions, including immune response and cellular repair.

Pharmacokinetics

The bioavailability of nutrients from fruits can vary based on the composition of the fruit and the individual's digestive health. Vitamins and antioxidants are typically absorbed in the small intestine, while dietary fiber is fermented in the colon. The metabolism of fruit-derived nutrients occurs through various pathways, with some compounds undergoing conjugation and excretion via the kidneys.

Pregnancy

Fruits are generally safe to consume during pregnancy and provide essential nutrients. However, certain fruits may need to be limited due to sugar content or potential allergies.

Breast-feeding

Fruits are safe to consume while breastfeeding and can contribute to the nutritional needs of both the mother and the infant. Some fruits may help with lactation.

Storage

Fruits should be stored in a cool, dry place, and refrigeration can help prolong freshness. Some fruits may require specific storage conditions to maintain quality.

Formulations

• whole fruit
• dried fruit
• fruit juice
• fruit puree
• fruit smoothie

Indications

• Nutritional supplementation
• Skin health enhancement
• Anti-inflammatory support
• Antioxidant therapy
• Boosting immune function

Dosage

Children: Refer to specific product formulations and guidelines as appropriate doses vary widely depending on the preparation and intended use.

Adults: Refer to specific product formulations and guidelines as appropriate doses vary widely depending on the preparation and intended use.

Mechanism of action

The active compounds in Hippophae, including flavonoids, carotenoids, and fatty acids, exert their effects through multiple mechanisms. They are known to scavenge free radicals, thereby reducing oxidative stress. Additionally, they may modulate inflammatory pathways by inhibiting the production of pro-inflammatory cytokines, enhancing the body's immune response. The presence of bioactive lipids also contributes to skin regeneration and repair.

Pharmacodynamics

Hippophae exhibits various pharmacodynamic properties, including anti-inflammatory, antioxidant, and skin-protective effects. Its constituents may influence cellular signaling pathways that regulate inflammation and cell survival. The antioxidant activity helps in protecting cells from oxidative damage, which is crucial in preventing chronic diseases and promoting health.

Pharmacokinetics

The pharmacokinetics of Hippophae have not been extensively studied in humans. However, it is known that the bioactive compounds are absorbed in the gastrointestinal tract. Metabolism may occur in the liver, and elimination pathways involve renal excretion. The bioavailability of its active components can be influenced by factors such as formulation and preparation methods.

Adverse effects

• Gastrointestinal discomfort
• Allergic reactions including rash and itching
• Headache

Precautions

• Use with caution in patients with known allergies to sea buckthorn or related products
• Monitor for potential gastrointestinal side effects

Pregnancy

Limited human data available. Use only if clearly needed and potential benefits justify the risks.

Breast-feeding

Limited data available. Caution is advised; consult a healthcare provider.

Storage

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

Formulations

• Oil
• Capsules
• Juice
• Topical preparations

Indications

• Metabolic acidosis
• Lactic acidosis
• Support in shock or severe dehydration
• Exercise physiology research

Dosage

Children: Refer to clinical guidelines for specific dosing recommendations based on the clinical condition being treated.

Adults: Refer to clinical guidelines for specific dosing recommendations based on the clinical condition being treated.

Mechanism of action

Lactic acid primarily functions by contributing to the acid-base balance in the body. It can serve as a substrate for gluconeogenesis in the liver and is utilized in the Cori cycle, where it is converted back to glucose. Furthermore, lactic acid can act as a signaling molecule in various physiological processes, influencing metabolism and cellular responses during hypoxic conditions.

Pharmacodynamics

Lactic acid dissociates into lactate and hydrogen ions in solution, which can lead to a decrease in pH (acidosis) when produced in excess. Its accumulation in the body is indicative of anaerobic metabolism, often observed during intense exercise or in conditions of oxygen deprivation. The body can buffer the effects of lactic acid through bicarbonate and other mechanisms, maintaining homeostasis.

Pharmacokinetics

Lactic acid is rapidly absorbed and distributed throughout the body. It is metabolized primarily in the liver, where it can be converted to glucose or further metabolized to carbon dioxide and water. The elimination half-life of lactate varies depending on the metabolic state of the individual and the presence of underlying conditions. Renal function also plays a role in the clearance of lactate from the body.

Adverse effects

• Nausea
• Vomiting
• Abdominal pain
• Diarrhea
• Hypersensitivity reactions

Precautions

• Use with caution in patients with renal impairment
• Monitor for signs of metabolic acidosis
• Caution in patients with liver disease

Pregnancy

Lactic acid is generally regarded as safe, but clinical use should be evaluated on a case-by-case basis during pregnancy.

Breast-feeding

Considered safe for use during breastfeeding, but consult healthcare provider for individual cases.

Storage

Store at room temperature, away from direct sunlight and moisture.

Formulations

• Lactic acid injection
• Lactic acid oral solution

Indications

• Insecticide for agricultural use
• Research tool in toxicology

Dosage

Children: Refer to the BNF for Children for specific dosing and administration guidelines.

Adults: Refer to the BNF for specific dosing and administration guidelines.

Mechanism of action

Methyl parathion acts primarily by inhibiting the enzyme acetylcholinesterase, which is essential for the breakdown of the neurotransmitter acetylcholine. Its active metabolite, methyl paraoxon, is a potent inhibitor of both acetylcholinesterase and butyrylcholinesterase. The inhibition of these enzymes results in the accumulation of acetylcholine at synapses, leading to overstimulation of cholinergic receptors and resultant toxic effects.

Pharmacodynamics

The pharmacodynamics of methyl parathion involve its action as a noncompetitive inhibitor of acetylcholinesterase, causing prolonged effects of acetylcholine due to its inability to be hydrolyzed. The resultant cholinergic toxicity can lead to symptoms such as muscle twitching, respiratory distress, and potentially fatal outcomes if not treated promptly. The extent of inhibition is dose-dependent, with significant toxicity occurring after substantial enzyme inhibition.

Pharmacokinetics

Methyl parathion is absorbed through the gastrointestinal tract and can also be absorbed through the skin and respiratory tract. It is metabolized in the liver to form methyl paraoxon, which is responsible for the majority of its toxic effects. The distribution of methyl parathion in body tissues is influenced by its lipophilicity, and it is primarily excreted as metabolites in the urine. The elimination half-life and specific pharmacokinetic parameters can vary based on individual metabolism and exposure levels.

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether this drug is excreted in human milk. Caution is advised when administering to nursing women.

Storage

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

Formulations

• Liquid formulation

Indications

• Hair conditioning
• Skin moisturization
• Improvement of hair manageability
• Reduction of static in hair

Dosage

Children: Polyquaternium-7 is generally considered safe for use in children when formulated in cosmetic products. Refer to specific product guidelines for appropriate usage.

Adults: Polyquaternium-7 is used in various concentrations in cosmetic formulations. Refer to specific product guidelines for appropriate usage.

Mechanism of action

Polyquaternium-7 works by electrostatically interacting with negatively charged sites on the hair and skin, forming a protective film that reduces friction and enhances moisture retention. This film-forming capability leads to improved texture and appearance of hair and skin, contributing to a smoother feel and reducing static.

Pharmacodynamics

Polyquaternium-7 exhibits conditioning effects by coating the hair shaft, which helps to reduce tangling and enhance shine. It is also effective in improving the feel of skin by providing a soft, smooth surface. Its anti-static properties prevent flyaway hair, making it a valuable ingredient in both hair and skin care formulations.

Pharmacokinetics

The pharmacokinetics of Polyquaternium-7 in terms of absorption, distribution, metabolism, and excretion have not been extensively studied, as it is primarily used topically. Due to its large molecular weight, it is not expected to be absorbed systemically. Its effects are localized to the application site, where it provides conditioning benefits without significant systemic exposure.

Adverse effects

• Skin irritation
• Allergic reactions

Precautions

• Avoid contact with eyes
• Discontinue use if irritation occurs

Pregnancy

Safety in pregnancy has not been established. Use only if clearly needed and prescribed by a healthcare provider.

Breast-feeding

Caution is advised. Consult a healthcare professional before use.

Storage

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

Formulations

• Topical solution
• Gel
• Cream

Indications

• Skin health
• Anti-inflammatory support
• Cardiovascular health
• Antioxidant supplementation
• Wound healing
• Digestive support
• Immune system support

Dosage

Children: Refer to specific product guidelines or consult a healthcare professional for appropriate dosing.

Adults: Refer to specific product guidelines or consult a healthcare professional for appropriate dosing.

Mechanism of action

Rhamnoides exhibits its effects primarily through its rich content of bioactive compounds, including flavonoids, carotenoids, and omega fatty acids. These compounds possess antioxidant properties that help to scavenge free radicals, thereby reducing oxidative stress and inflammation in the body. The anti-inflammatory effects of rhamnoides may also be attributed to modulation of inflammatory pathways such as the NF-kB signaling pathway.

Pharmacodynamics

The pharmacodynamics of rhamnoides are primarily related to its antioxidant capacity and its ability to influence lipid metabolism. The antioxidants in rhamnoides can enhance cellular health by protecting cells from oxidative damage. Additionally, it may improve skin hydration and elasticity, and support immune function. The anti-inflammatory properties can help in conditions such as arthritis and skin disorders.

Pharmacokinetics

The pharmacokinetics of rhamnoides are not extensively studied, but its bioactive compounds are believed to be absorbed in the gastrointestinal tract after ingestion. The absorption and bioavailability of these compounds can vary based on formulation and individual differences. Metabolism may occur in the liver, with excretion primarily through urine and feces. Further research is needed to fully elucidate the pharmacokinetics of rhamnoides.

Pregnancy

There is limited data on the safety of rhamnoides during pregnancy. Consult a healthcare professional before use.

Breast-feeding

There is insufficient information on the excretion of rhamnoides in human milk. Caution is advised when administering to breastfeeding women.

Storage

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

Indications

• Constipation
• Diagnostic aid in colonoscopy preparation
• Management of hyperosmolality in various conditions

Dosage

Children: For children, the dosage should be determined based on age and condition, and it is advised to refer to the BNF for Children for specific dosing guidelines.

Adults: The typical dose for adults is 30 to 150 mL of sorbitol solution (70%) taken orally, as needed, usually before bedtime.

Mechanism of action

Sorbitol exerts its laxative effect by drawing water into the large intestine, thereby stimulating bowel movements. It acts as a hygroscopic agent, pulling water from tissues into the feces, which reflexively stimulates evacuation. In metabolic pathways, sorbitol is produced from glucose via aldose reductase and is converted to fructose by sorbitol dehydrogenase, with implications in diabetic complications such as retinopathy.

Pharmacodynamics

Sorbitol's laxative effect results from its osmotic properties, which increase the water content of the stool and soften it, facilitating easier passage. Additionally, sorbitol can induce apoptosis in certain cancer cell lines, indicating potential therapeutic implications beyond its laxative use. The modulation of intracellular signaling pathways through the regulation of proteins such as Bax and Bcl-2 suggests a complex role in cellular health and disease.

Pharmacokinetics

Sorbitol is poorly absorbed in the gastrointestinal tract, which contributes to its efficacy as a laxative. It is metabolized in the liver, primarily through the polyol pathway. The absorption and distribution of sorbitol are affected by its osmotic properties, leading to increased intestinal water retention. Its elimination is primarily via renal excretion, with minimal systemic absorption, thus reducing the risk of systemic side effects.

Adverse effects

• Diarrhea
• Abdominal cramps
• Nausea
• Vomiting
• Electrolyte imbalances

Precautions

• Use with caution in patients with renal impairment
• May exacerbate gastrointestinal conditions

Pregnancy

Sorbitol is generally considered safe during pregnancy, but should be used under medical supervision.

Breast-feeding

Sorbitol is excreted in breast milk in small amounts; consult a healthcare provider before use.

Storage

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

Formulations

• Oral solution
• Syrup

Indications

• Anti-inflammatory
• Antioxidant
• Antimicrobial
• Wound healing
• Pain relief
• Nutritional support

Dosage

Children: Paediatric dosing for tree-derived substances is highly variable and should be determined by a healthcare professional. Specific recommendations depend on the tree species and the health condition being addressed.

Adults: Dosage for tree-derived substances varies widely based on the specific product and its intended use. It is important to refer to the manufacturer's guidelines or consult with a healthcare professional for appropriate dosing.

Mechanism of action

The mechanism of action for tree-derived compounds varies widely depending on the specific chemical constituents present in the parts used. Many tree extracts contain flavonoids, terpenoids, alkaloids, and tannins, which can exhibit anti-inflammatory, antioxidant, antimicrobial, and anti-cancer properties through various biochemical pathways. These compounds may modulate the immune response, inhibit oxidative stress, or interfere with cellular signaling pathways.

Pharmacodynamics

Pharmacodynamics of tree-derived compounds can include effects such as modulation of inflammation, enhancement of immune function, and reduction of oxidative stress. Certain compounds can also influence neurotransmitter systems, providing potential benefits in mood disorders. The efficacy and safety profiles are highly dependent on the species and part of the tree used, as well as the preparation method.

Pharmacokinetics

The pharmacokinetics of tree-derived substances vary greatly. Factors such as solubility, absorption, distribution, metabolism, and excretion can be influenced by the specific compounds and their formulations. Generally, tree extracts may demonstrate variable bioavailability due to differences in extraction methods and the presence of other active constituents that can enhance or inhibit absorption.

Pregnancy

Not well-studied; consult with a healthcare professional.

Breast-feeding

Not well-studied; consult with a healthcare professional.

Storage

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

Mechanism of action

Homocystinuria is a hereditary disorder characterized by high levels of the amino acid homocysteine. This condition can be caused by deficiencies or defects in cystathionine beta-synthase (CBS), 5,10-methylenetetrahydrofolate reductase (MTHFR), and cobalamin cofactor metabolism (cbl). CBS converts homocysteine to cystathionine, and a deficiency in this enzyme can lead to an accumulation of homocysteine. MTHFR is responsible for producing 5-methyltetrahydrofolate, a methyl donor that participates in the conversion of homocysteine back to methionine; therefore, an MTHFR deficiency can also lead to homocystinuria. Additionally, a defect in cobalamin (vitamin B12) cofactor metabolism can lead to homocystinuria, since a metabolite of cobalamin (methylcobalamin) promotes the conversion of homocysteine to methionine. Betaine transfers a methyl group via the enzyme betaine homocysteine methyl transferase (BHMT), converting homocysteine back into methionine and dimethylglycine (DMG). In patients with homocystinuria, betaine reduces homocysteine levels and improves health outcomes. Betaine acts as metabolic intermediate in transmethylating processes (creatine and methionine synthesis). Betaine acts as a methyl group donor in the remethylation of homocysteine to methionine in patients with homocystinuria. This reduces toxic concentrations of homocysteine, usually to 20 to 30% or less of pretreatment concentrations. Betaine or trimethylglycine is a quarternary ammonium compound that was first discovered in the juice of sugar beets (Beta vulgaris). Betaine is a metabolite of choline ... and is a substrate in one of the two recycling pathways that convert homocysteine to L-methionine. The other and principal recycling reaction is catalyzed by the enzyme methionine synthase and uses methylcobalamin as a cofactor and 5-methyltetrahydrofolate as a cosubstrate. Betaine-homocysteine methyltransferase (BHMT) is a zinc metalloenzyme which catalyzes the transfer of a methyl group from betaine to homocysteine in the formation of methionine. BHMT is found in the liver and kidneys and may also exist in brain tissue. Betaine acts to lower homocysteine levels in some with primary hyperhomocysteinemia/homocystinuria via this enzyme.

Pharmacodynamics

Betaine decreases plasma homocysteine concentrations in homocystinuria cases caused by deficiencies or defects in cystathionine beta-synthase (CBS), 5,10-methylenetetrahydrofolate reductase (MTHFR), and cobalamin cofactor metabolism (cbl). The decrease of homocysteine is estimated to be 20-30% of pre-treatment levels. Betaine supplementation in patients with homocystinuria also improves metabolic abnormalities in cerebrospinal fluid. Reports have shown that depending on the type of homocystinuria, the therapeutic effectiveness of betaine alone may be limited, insufficient to decrease total homocysteine levels and prevent clinical symptoms. In patients with homocystinuria due to cystathionine beta-synthase (CBS) deficiency, betaine should be used when serum total homocysteine levels remain high despite dietary therapy. Patients taking betaine for several years do not show evidence of tolerance. Also, betaine concentrations are not correlated with homocysteine concentrations. In patients with MTHFR deficiency and cbl defects, betaine may increase methionine and S-adenosyl methionine (SAM) plasma levels. Patients with CBS deficiency without a dietary restriction of methionine may accumulate excessive amounts of methionine. Clinical data shows that in patients with CBS deficiency, increased plasma methionine levels were associated with cerebral edema.

Mechanism of action

Dexpanthenol is an alcohol derivative of pantothenic acid, a component of the B complex vitamins and an essential component of a normally functioning epithelium. Dexpanthenol is enzymatically cleaved to form pantothenic acid, which is an essential component of Coenzyme A, which acts as a cofactor in many enzymatic reactions that are important for protein metabolism in the epithelium. Dermatological effects of the topical use of dexpanthenol include increased fibroblast proliferation and accelerated re-epithelialization in wound healing. Furthermore, it acts as a topical protectant, moisturizer, and has demonstrated anti-inflammatory properties. This alcohol ... is said to increase the amount of coenzyme A available for the synthesis of acetylcholine. Increased formation of acetylcholine is thought to increase peristalsis and intestinal tone. ... To test the functional effect of pantothenate on dermal fibroblasts, cells were cultured and in vitro proliferation tests were performed using a standardized scratch test procedure. For all three donors analyzed, a strong stimulatory effect of pantothenate at a concentration of 20 ug/mL on the proliferation of cultivated dermal fibroblasts was observed. To study the molecular mechanisms resulting in the proliferative effect of pantothenate, gene expression was analyzed in dermal fibroblasts cultivated with 20 ug/mL of pantothenate compared with untreated cells using the GeneChip Human Exon 1.0 ST Array. A number of significantly regulated genes were identified including genes coding for interleukin (IL)-6, IL-8, Id1, HMOX-1, HspB7, CYP1B1 and MARCH-II. Regulation of these genes was subsequently verified by quantitative real-time polymerase chain reaction analysis. Induction of HMOX-1 expression by pantothenol and pantothenic acid in dermal cells was confirmed on the protein level using immunoblots. Functional studies revealed the enhanced suppression of free radical formation in skin fibroblasts cultured with panthenol. In conclusion, these studies provided new insight in the molecular mechanisms linked to the stimulatory effect of pantothenate and panthenol on the proliferation of dermal fibroblasts. /Calcium pantotenate/ ... Pantothenic acid, pantothenol and other derivatives ... are precursors of CoA /that/ protect cells and whole organs against peroxidative damage by increasing the content of cell glutathione...

Pharmacodynamics

Pantothenic acid is a precursor of coenzyme A, which serves as a cofactor for a variety of enzyme-catalyzed reactions involving transfer of acetyl groups. The final step in the synthesis of acetylcholine consists of the choline acetylase transfer of acetyl group from acetylcoenzyme A to choline. Acetylcholine is the neurohumoral transmitter in the parasympathetic system and as such maintains the normal functions of the intestine. Decrease in acetylcholine content would result in decreased peristalsis and in extreme cases adynamic ileus.

Mechanism of action

Acute poisoning ... is related to ... inhibiting action on enzyme acetylcholinesterase. Toxic manifestations generally occur only after more than 50% of plasma cholinesterase is inhibited. ... Methyl parathion ... depend on oxidative activation by replacement of thiono-sulfur with oxygen for ... toxicity. Methyl parathion has only a slight inhibitory action on acetylcholinesterase and butyrylcholinesterase, but its active metabolite, methyl paraoxon, is a potent inhibitor of both these enzymes. A study was conducted examining the inhibition of (Ca2+ and Mg2+)-ATPase by parathion (56382) and methyl parathion. Enzyme activity was assessed spectrophotometrically in pig erythrocyte membranes containing calcium2+ (Ca2+) and magnesium2+ and in solubilized membrane preparations incubated with the test agents. The enzyme response to ATP was biphasic. Equations expressing the kinetics of the substrate curves described two classes of the ATP binding active site, one with high affinity and low maximum rate and one with low affinity and high maximum rate. High affinity active sites were stimulated by low ATP concentrations (20 uM), whereas low affinity active sites were stimulated by high ATP levels (2 mM). Parathion and methylparathion dose dependently inhibited enzyme activity; parathion had a greater inhibitory effect than methylparathion. Lineweaver-Burke and Dixon plots indicated noncompetitive inhibition. Parathion and methylparathion induced enzyme inhibition occurred over a range of free calcium ion concentrations (0.5 to 5 mM); the inhibition was significantly greater at lower Ca2+ concentrations (1 to 100 uM) than at higher concentrations. The authors conclude that parathion and methylparathion inhibit ATPase activity by binding to a site on the enzyme rather than through an interaction with associated lipids. For more Mechanism of Action (Complete) data for METHYL PARATHION (6 total), please visit the HSDB record page.

Mechanism of action

Sorbitol exerts its laxative effect by drawing water into the large intestine, thereby stimulating bowel movements. ... Sorbitol exerts hygroscopic and/or local irritant action, drawing water from tissues into feces and reflexly stimulating evacuation. The polyol pathway consists of two enzymes aldose reductase (AR) and sorbitol dehydrogenase (SDH); the former is the first enzyme in the polyol pathway, that catalyzes the reduction of glucose to sorbitol, the latter is the second one, that converts sorbitol to fructose using by NAD(+) as a cofactor. ... SDH activity, the second step in the polyol pathway, might make a greater contribution to the etiology of diabetic retinopathy than does the first step involving AR. /This paper proposes/ a novel hypothesis that polymorphisms of SDH gene may be correlated with SDH gene expression levels in diabetic retinas, thus being a valuable genetic marker for diabetic retinopathy. It has been reported that sorbitol induces apoptosis in several cancer cell lines. ... In /this/ study, the intracellular signaling pathways of sorbitol-induced apoptosis in human K562 cells were investigated using both morphological analysis and DNA fragmentation technique. In this study, we demonstrated that sorbitol-induced apoptosis in human K562 cells is a concentration- and time-dependent manner. This sorbitol-induced apoptosis in human K562 cells was also accompanied by the up-regulation of Bax, and down-regulation of p-Bcl-2, but no effect on the levels of Bcl-X(L). Moreover, the sorbitol treatment resulted in a significant reduction of mitochondria membrane potential, increase in the release of mitochondrial cytochrome c (cyt c), and activation of caspase 3. Furthermore, treatment with caspase 3 inhibitor (z-DEVD-fmk) was capable of preventing the sorbitol-induced caspase 3 activity and cell death. These results clearly demonstrate that the induction of apoptosis by sorbitol involves multiple cellular/molecular pathways and strongly suggest that pro- and anti-apoptotic Bcl-2 family proteins, mitochondrial membrane potential, mitochondrial cyt c, and caspase 3, they all participate in sorbitol-induced apoptotic process in human K562 cells. Chronic diabetic complications, in particular, nephropathy, peripheral and autonomic neuropathy, "diabetic foot," retinopathy, and cardiovascular disease, remain the major cause of morbidity and mortality in patients with diabetes mellitus. Growing evidence indicates that both increased activity of the sorbitol pathway of glucose metabolism and enhanced oxidative stress are the leading factors in the pathogenesis of diabetic complications. The relation between the two mechanisms remains the area of controversy. One group has reported that increased sorbitol pathway activity has a protective rather than detrimental role in complication-prone tissues because the pathway detoxifies toxic lipid peroxidation products. Others put forward a so-called "unifying hypothesis" suggesting that activation of several major pathways implicated in diabetic complications (eg, sorbitol pathway) occurs due to increased production of superoxide anion radicals in mitochondria and resulting poly(ADP-ribose) polymerase activation. This review (a) presents findings supporting a key role for the sorbitol pathway in oxidative stress and oxidative stress-initiated downstream mechanisms of diabetic complications, and (b) summarizes experimental evidence against a detoxifying role of the sorbitol pathway, as well as the "unifying concept."