Rhodamines
Rhodamine 123
Fluorescent Dyes
Xanthenes
P-Glycoprotein
Drug Resistance, Multiple
Fluoresceins
Fluorescein
Microscopy, Fluorescence
Genes, MDR
Mitochondria
Phalloidine
Drug Resistance, Multiple, Fungal
Sodium Azide
Biological Transport
Retrograde Obturation
P-Glycoproteins
Staining and Labeling
Fluorescence
Microscopy, Confocal
Carbocyanines
Gossypol
Flow Cytometry
Energy Transfer
Coloring Agents
Daunorubicin
Fluorescence Polarization
ATP-Binding Cassette Transporters
Cyclosporins
Multidrug Resistance-Associated Proteins
Bcl-xL prevents cell death following growth factor withdrawal by facilitating mitochondrial ATP/ADP exchange. (1/403)
Growth factor withdrawal is associated with a metabolic arrest that can result in apoptosis. Cell death is preceded by loss of outer mitochondrial membrane integrity and cytochrome c release. These mitochondrial events appear to follow a relative increase in mitochondrial membrane potential. This change in membrane potential results from the failure of the adenine nucleotide translocator (ANT)/voltage-dependent anion channel (VDAC) complex to maintain ATP/ADP exchange. Bcl-xL expression allows growth factor-deprived cells to maintain sufficient mitochondrial ATP/ADP exchange to sustain coupled respiration. These data demonstrate that mitochondrial adenylate transport is under active regulation. Efficient exchange of ADP for ATP is promoted by Bcl-xL expression permitting oxidative phosphorylation to be regulated by cellular ATP/ADP levels and allowing mitochondria to adapt to changes in metabolic demand. (+info)Transport of rhodamine 123, a P-glycoprotein substrate, across rat intestine and Caco-2 cell monolayers in the presence of cytochrome P-450 3A-related compounds. (2/403)
Effects of cytochrome P-450 3A- and P-glycoprotein (P-gp)-related compounds, erythromycin, midazolam, ketoconazole, verapamil, and quinidine, on transport of rhodamine 123 (Rho-123), a P-gp substrate, were studied in rat intestine and in Caco-2 cells. Ileum was mainly used in rat studies because this segment showed greater P-gp-mediated Rho-123 transport. In an in vitro everted rat ileum, all the compounds examined significantly inhibited the transport of Rho-123 from serosal to mucosal surfaces across the intestine, with different inhibitory potencies among these compounds. In an in vivo rat study, the exsorption of Rho-123 from blood to the intestinal lumen, which was evaluated as exsorption clearance of Rho-123 under a steady-state plasma concentration of Rho-123, was also inhibited when these compounds were added to the intestinal lumen. Similarly, transepithelial transport of Rho-123 from the basolateral to apical side across Caco-2 cell monolayers was inhibited by these compounds. A linear relationship was observed in their inhibitory potencies on Rho-123 transport between in vitro and in vivo studies using rat ileum and between studies with rat ileum and Caco-2 cells. P-gp-mediated transport across the intestine was found to be inhibited not only by P-gp-related but also by all the cytochrome P-450 3A-related compounds examined. Within experimental error, the relative inhibitory potencies were the same between the studies with rat ileum (in vivo, in vitro) and those with Caco-2 cells. Thus, it is suggested that the function of P-gp and its sensitivity to these drugs may be similar in rat intestine and Caco-2 cells. (+info)Stimulation of P-glycoprotein-mediated drug transport by prazosin and progesterone. Evidence for a third drug-binding site. (3/403)
P-glycoprotein is a plasma membrane protein of mammalian cells that confers multidrug resistance by acting as a broad-specificity, ATP-dependent efflux transporter of diverse lipophilic neutral or cationic compounds. Previously, we identified two positively cooperative drug-binding sites of P-glycoprotein involved in transport [Shapiro, A. B. & Ling, V. (1997) Eur. J. Biochem. 250, 130-137]. The H site is selective for Hoechst 33342 and colchicine. The R site is selective for rhodamine 123 and anthracyclines. Substrate binding to one site stimulates transport by the other. In this paper, we show that prazosin and progesterone stimulate the transport of both Hoechst 33342 and rhodamine 123. Rhodamine 123 and prazosin (or progesterone) in combination stimulate Hoechst 33342 transport in an additive manner. In contrast, Hoechst 33342 and either prazosin or progesterone interfere with each other, so that the stimulatory effect of the combination on rhodamine 123 transport is less than that of each individually. Non-P-glycoprotein-specific effects of prazosin on membrane fluidity and permeability were excluded. These results indicate the existence of a third drug-binding site on P-glycoprotein with a positive allosteric effect on drug transport by the H and R sites. This allosteric site appears to be one of the sites of photoaffinity labeling of P-glycoprotein by [125I]iodoarylazidoprazosin [Safa, A. R., Agresti, M., Bryk, D. & Tamai, I. (1994) Biochemistry 33, 256-265] and is likely not to be capable of drug transport. (+info)Oxidant-induced apoptosis in cultured human retinal pigment epithelial cells. (4/403)
PURPOSE: To determine the mechanism of oxidant-induced cell death in cultured human retinal pigment epithelium (hRPE). METHODS: Cultured hRPE cells were treated with different concentrations of a chemical oxidant, t-butylhydroperoxide (tBH), for different periods of time. Apoptosis was determined with terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) and flow cytometry. Mitochondrial membrane potential (mtdelta psi) was measured by rhodamine 123 staining and subsequent flow cytometry. Release of mitochondrial cytochrome c (cyt c) and cleavage of procaspase 3 and caspase substrates were determined by western blot analysis. RESULTS: t-Butylhydroperoxide caused time- and dose-dependent activation of apoptosis in hRPE, indicated by characteristic morphologic changes; TUNEL-positive labeling; phosphatidylserine (PS) exposure; and procaspase 3, poly(ADP-ribose)polymerase, lamin, and tubulin cleavage. An early decrease of mtdelta psi was observed before caspase activation, together with the release of mitochondrial cyt c. CONCLUSIONS: Results indicate that tBH can induce apoptosis in hRPE, probably by triggering the mitochondrial permeability transition, which results in swelling and release of mitochondrial intermembrane proteins. (+info)Uncouplers of oxidative phosphorylation can enhance a Fas death signal. (5/403)
Recent work suggests a participation of mitochondria in apoptotic cell death. This role includes the release of apoptogenic molecules into the cytosol preceding or after a loss of mitochondrial membrane potential DeltaPsim. The two uncouplers of oxidative phosphorylation carbonyl cyanide m-chlorophenylhydrazone (CCCP) and 2, 4-dinitrophenol (DNP) reduce DeltaPsim by direct attack of the proton gradient across the inner mitochondrial membrane. Here we show that both compounds enhance the apoptosis-inducing capacity of Fas/APO-1/CD95 signaling in Jurkat and CEM cells without causing apoptotic changes on their own account. This amplification occurred upstream or at the level of caspases and was not inhibited by Bcl-2. The effect could be blocked by the cowpox protein CrmA and is thus likely to require caspase 8 activity. Apoptosis induction by staurosporine in Jurkat cells as well as by Fas in SKW6 cells was unaffected by CCCP and DNP. The role of cytochrome c during Fas-DNP signaling was investigated. No early cytochrome c release from mitochondria was detected by Western blotting. Functional assays with cytoplasmic preparations from Fas-DNP-treated cells also indicated that there was no major contribution by cytochrome c or caspase 9 to the activation of effector caspases. Furthermore, an increase of rhodamine-123 uptake into intact cells, which has been explained by mitochondrial swelling, occurred considerably later than the caspase activation and was blocked by Z-VAD-fmk. These data show that uncouplers of oxidative phosphorylation can presensitize some but not all cells for a Fas death signal and provide information about the existence of separate pathways in the induction of apoptosis. (+info)Bioenergetic and structural consequences of allotopic expression of subunit 8 of yeast mitochondrial ATP synthase. The hydrophobic character of residues 23 and 24 is essential for maximal activity and structural stability of the enzyme complex. (6/403)
Subunit 8 (Y8), a mitochondrially encoded subunit of the F0 sector of the F1F0-ATP synthase is essential for oxidative phosphorylation. We have previously introduced the technique of allotopic expression to study the structure/function of Y8, whereby an artificial Y8 gene is expressed in the nucleus of cells lacking a functional mitochondrial Y8, thus generating assembly of a functional F1F0-ATPase complex. In this paper we show that when a gene encoding an essentially unmodified version of Y8 is allotopically expressed, ATP synthesis and hydrolysis rates, as well as efficiency of oxidative phosphorylation, were similar to those of the parental wild-type strain in which Y8 is naturally expressed in mitochondria. We then tested the requirement for the hydrophobicity of the central domain (residues 14-32), which possibly represents a transmembrane stem, by introducing adjacent negative charges at different positions of Y8. One of the variants thus generated, which carries the double substitution Leu23-->Asp, Leu24-->Asp, when expressed in a strain lacking endogenous Y8, gave rise to cells which grew very slowly by oxidative phosphorylation. Measurement of bioenergetic parameters showed two major defects in these cells relative to control cells allotopically expressing unmodified Y8. First, the activity of the F1F0-ATP synthase was significantly decreased. ATP synthesis and state 3 of respiration were reduced by approximately 30-40%. ATP hydrolysis was reduced by approximately 30% and was almost insensitive to the F0 inhibitor oligomycin. Second, the physical coupling between the two sectors of the enzyme, as well as the stability of the F1 sector itself, were affected as shown by decreased recovery of F0 sector [8, 9, b, oligomycin sensitivity-conferring protein (OSCP), d, h and f] and F1 sector (alpha, gamma, delta) subunits in immunoprecipitates of ATP synthase. This study indicates that Y8 not only performs an important role in the structure of the mitochondrial complex but also in its activity. We conclude that the hydrophobic character of amino acids 23 and 24 in the middle of the putative transmembrane stem of Y8 is essential for coupling proton transport through F0 to ATP synthesis on F1. (+info)Inhibition of P-glycoprotein-mediated transport by a hydrophobic contaminant in commercial gluconate salts. (7/403)
The substitution of gluconate for Cl- is commonly used to characterize Cl- transport or Cl--dependent transport mechanisms. We evaluated the effects of substituting gluconate for Cl- on the transport of the P-glycoprotein substrate rhodamine 123 (R123). The replacement of Ringer solution containing Cl- (Cl--Ringer) with gluconate-Ringer inhibited R123 efflux, whereas the replacement of Cl- by other anions (sulfate or cyclamate) had no effect. The inhibition of R123 efflux by gluconate-Ringer was absent after chloroform extraction of the sodium gluconate salt. The readdition of the sodium gluconate-chloroform extract to the extracted gluconate-Ringer or to cyclamate-Ringer inhibited R123 efflux, whereas its addition to Cl--Ringer had no effect. These observations indicate that the inhibition of P-glycoprotein-mediated R123 transport by gluconate is due to one or more chloroform-soluble contaminants and that the inhibition is absent in the presence of Cl-. The results are consistent with the fact that P-glycoprotein substrates are hydrophobic. Care should be taken when replacing ions to evaluate membrane transport mechanisms because highly pure commercial preparations may still contain potent contaminants that affect transport. (+info)Short-term block of Na+/K+-ATPase in neuro-glial cell cultures of cerebellum induces glutamate dependent damage of granule cells. (8/403)
Granule cells in a dissociated neuro-glial cell culture of cerebellum when exposed to ouabain (10(-3) M) for 25 min apparently swell, increase their [Ca2+]i with obvious depolarization of the mitochondrial membrane. In 3 h after ouabain was omitted from the solution, 62 +/- 3% of granule cells had pycnotic nuclei. The supplement of a solution with competitive specific antagonist of NMDA receptors, L-2-amino-7-phosphonoheptanoate (10(-4) M, APH) together with ouabain prevented cells from swelling, mitochondrial deenergization, neuronal death and increase of [Ca2+]i. These data suggest that cellular Na+/K+-ATPase inactivation in neuro-glial cell cultures of cerebellum leads to glutamate (Glu) accumulation, hyperstimulation of glutamate receptors, higher Ca2+ and Na+ influxes into the cells through the channels activated by Glu. This process leads to cell swelling, mitochondrial deenergization and death of granule cells. Possibly, the decrease of Na+/K+-ATPase activity in brain cells can lead to the onset of at least some chronic neurological disorders. (+info)Rhodamines are not a medical term, but rather a class of chemical compounds that are commonly used as dyes and fluorescent tracers in various fields, including biology, chemistry, and material science. They absorb light at one wavelength and emit it at another, longer wavelength, which makes them useful for tracking and visualizing processes in living cells and tissues.
In a medical context, rhodamines may be used as part of diagnostic tests or procedures, such as in fluorescence microscopy or flow cytometry, to label and detect specific cells or molecules of interest. However, they are not typically used as therapeutic agents themselves.
Rhodamine 123 is not a medical term, but a chemical compound. It's a fluorescent dye used in various scientific and research applications, particularly in the field of cell biology. Rhodamine 123 has an affinity for mitochondria, the energy-producing structures in cells, making it useful as a marker to study mitochondrial function and distribution within cells.
In summary, Rhodamine 123 is not a medical definition itself, but it can be used in medical research contexts to investigate cellular processes.
Fluorescent dyes are substances that emit light upon excitation by absorbing light of a shorter wavelength. In a medical context, these dyes are often used in various diagnostic tests and procedures to highlight or mark certain structures or substances within the body. For example, fluorescent dyes may be used in imaging techniques such as fluorescence microscopy or fluorescence angiography to help visualize cells, tissues, or blood vessels. These dyes can also be used in flow cytometry to identify and sort specific types of cells. The choice of fluorescent dye depends on the specific application and the desired properties, such as excitation and emission spectra, quantum yield, and photostability.
Xanthenes are a class of organic compounds that contain a xanthene core, which is a tricyclic compound made up of two benzene rings fused to a central pyran ring. They have the basic structure:
While xanthenes themselves do not have significant medical applications, many of their derivatives are widely used in medicine and research. For example, fluorescein and eosin are xanthene dyes that are commonly used as diagnostic tools in ophthalmology and as stains in histology. Additionally, some xanthene derivatives have been explored for their potential therapeutic benefits, such as anti-inflammatory, antimicrobial, and anticancer activities. However, it is important to note that individual medical definitions would depend on the specific xanthene derivative in question.
P-glycoprotein (P-gp) is a type of membrane transport protein that plays a crucial role in the efflux (extrusion) of various substrates, including drugs and toxins, out of cells. It is also known as multidrug resistance protein 1 (MDR1).
P-gp is encoded by the ABCB1 gene and is primarily located on the apical membrane of epithelial cells in several tissues, such as the intestine, liver, kidney, and blood-brain barrier. Its main function is to protect these organs from harmful substances by actively pumping them out of the cells and back into the lumen or bloodstream.
In the context of pharmacology, P-gp can contribute to multidrug resistance (MDR) in cancer cells. When overexpressed, P-gp can reduce the intracellular concentration of various anticancer drugs, making them less effective. This has led to extensive research on inhibitors of P-gp as potential adjuvants for cancer therapy.
In summary, P-glycoprotein is a vital efflux transporter that helps maintain homeostasis by removing potentially harmful substances from cells and can impact drug disposition and response in various tissues, including the intestine, liver, kidney, and blood-brain barrier.
"Multiple drug resistance" (MDR) is a term used in medicine to describe the condition where a patient's infection becomes resistant to multiple antimicrobial drugs. This means that the bacteria, virus, fungus or parasite that is causing the infection has developed the ability to survive and multiply despite being exposed to medications that were originally designed to kill or inhibit its growth.
In particular, MDR occurs when an organism becomes resistant to at least one drug in three or more antimicrobial categories. This can happen due to genetic changes in the microorganism that allow it to survive in the presence of these drugs. The development of MDR is a significant concern for public health because it limits treatment options and can make infections harder, if not impossible, to treat.
MDR can develop through several mechanisms, including mutations in the genes that encode drug targets or enzymes involved in drug metabolism, as well as the acquisition of genetic elements such as plasmids and transposons that carry resistance genes. The overuse and misuse of antimicrobial drugs are major drivers of MDR, as they create selective pressure for the emergence and spread of resistant strains.
MDR infections can occur in various settings, including hospitals, long-term care facilities, and communities. They can affect people of all ages and backgrounds, although certain populations may be at higher risk, such as those with weakened immune systems or chronic medical conditions. Preventing the spread of MDR requires a multifaceted approach that includes surveillance, infection control, antimicrobial stewardship, and research into new therapies and diagnostics.
Fluorescein is not a medical condition, but rather a diagnostic dye that is used in various medical tests and procedures. It is a fluorescent compound that absorbs light at one wavelength and emits light at another wavelength, which makes it useful for imaging and detecting various conditions.
In ophthalmology, fluorescein is commonly used in eye examinations to evaluate the health of the cornea, conjunctiva, and anterior chamber of the eye. A fluorescein dye is applied to the surface of the eye, and then the eye is examined under a blue light. The dye highlights any damage or abnormalities on the surface of the eye, such as scratches, ulcers, or inflammation.
Fluorescein is also used in angiography, a medical imaging technique used to examine blood vessels in the body. A fluorescein dye is injected into a vein, and then a special camera takes pictures of the dye as it flows through the blood vessels. This can help doctors diagnose and monitor conditions such as cancer, diabetes, and macular degeneration.
Overall, fluorescein is a valuable diagnostic tool that helps medical professionals detect and monitor various conditions in the body.
Fluorescein is not a medical condition or term, but rather a diagnostic dye used in various medical tests and procedures. Medically, it is referred to as Fluorescein Sodium, a fluorescent compound that absorbs light at one wavelength and emits light at another longer wavelength when excited.
In the field of ophthalmology (eye care), Fluorescein is commonly used in:
1. Fluorescein angiography: A diagnostic test to examine blood flow in the retina and choroid, often used to diagnose and manage conditions like diabetic retinopathy, age-related macular degeneration, and retinal vessel occlusions.
2. Tear film assessment: Fluorescein dye is used to evaluate the quality of tear film and diagnose dry eye syndrome by observing the staining pattern on the cornea.
3. Corneal abrasions/foreign body detection: Fluorescein dye can help identify corneal injuries, such as abrasions or foreign bodies, under a cobalt blue light.
In other medical fields, fluorescein is also used in procedures like:
1. Urinary tract imaging: To detect urinary tract abnormalities and evaluate kidney function.
2. Lymphangiography: A procedure to visualize the lymphatic system.
3. Surgical navigation: In some surgical procedures, fluorescein is used as a marker for better visualization of specific structures or areas.
Verapamil is a calcium channel blocker medication that is primarily used to treat hypertension (high blood pressure), angina (chest pain), and certain types of cardiac arrhythmias (irregular heart rhyats). It works by relaxing the smooth muscle cells in the walls of blood vessels, which causes them to dilate or widen, reducing the resistance to blood flow and thereby lowering blood pressure. Verapamil also slows down the conduction of electrical signals within the heart, which can help to regulate the heart rate and rhythm.
In addition to its cardiovascular effects, verapamil is sometimes used off-label for the treatment of other conditions such as migraine headaches, Raynaud's phenomenon, and certain types of tremors. It is available in various forms, including immediate-release tablets, extended-release capsules, and intravenous (IV) injection.
It is important to note that verapamil can interact with other medications, so it is essential to inform your healthcare provider about all the drugs you are taking before starting this medication. Additionally, verapamil should be used with caution in people with certain medical conditions, such as heart failure, liver disease, and low blood pressure.
Fluorescence microscopy is a type of microscopy that uses fluorescent dyes or proteins to highlight and visualize specific components within a sample. In this technique, the sample is illuminated with high-energy light, typically ultraviolet (UV) or blue light, which excites the fluorescent molecules causing them to emit lower-energy, longer-wavelength light, usually visible light in the form of various colors. This emitted light is then collected by the microscope and detected to produce an image.
Fluorescence microscopy has several advantages over traditional brightfield microscopy, including the ability to visualize specific structures or molecules within a complex sample, increased sensitivity, and the potential for quantitative analysis. It is widely used in various fields of biology and medicine, such as cell biology, neuroscience, and pathology, to study the structure, function, and interactions of cells and proteins.
There are several types of fluorescence microscopy techniques, including widefield fluorescence microscopy, confocal microscopy, two-photon microscopy, and total internal reflection fluorescence (TIRF) microscopy, each with its own strengths and limitations. These techniques can provide valuable insights into the behavior of cells and proteins in health and disease.
"MDR" is an abbreviation for "Multidrug Resistance." In the context of genetics, MDR genes are those that encode for proteins, typically transmembrane pumps, which can actively transport various drugs out of cells. This results in reduced drug accumulation within cells and decreased effectiveness of these drugs.
MDR genes play a crucial role in conferring resistance to chemotherapy agents in cancer cells, making treatment more challenging. One well-known MDR gene is the ABCB1 (ATP Binding Cassette Subfamily B Member 1) gene, which encodes for the P-glycoprotein efflux pump. Overexpression of such MDR genes can lead to cross-resistance to multiple drugs, further complicating treatment strategies.
Fluorescence spectrometry is a type of analytical technique used to investigate the fluorescent properties of a sample. It involves the measurement of the intensity of light emitted by a substance when it absorbs light at a specific wavelength and then re-emits it at a longer wavelength. This process, known as fluorescence, occurs because the absorbed energy excites electrons in the molecules of the substance to higher energy states, and when these electrons return to their ground state, they release the excess energy as light.
Fluorescence spectrometry typically measures the emission spectrum of a sample, which is a plot of the intensity of emitted light versus the wavelength of emission. This technique can be used to identify and quantify the presence of specific fluorescent molecules in a sample, as well as to study their photophysical properties.
Fluorescence spectrometry has many applications in fields such as biochemistry, environmental science, and materials science. For example, it can be used to detect and measure the concentration of pollutants in water samples, to analyze the composition of complex biological mixtures, or to study the properties of fluorescent nanomaterials.
Mitochondria are specialized structures located inside cells that convert the energy from food into ATP (adenosine triphosphate), which is the primary form of energy used by cells. They are often referred to as the "powerhouses" of the cell because they generate most of the cell's supply of chemical energy. Mitochondria are also involved in various other cellular processes, such as signaling, differentiation, and apoptosis (programmed cell death).
Mitochondria have their own DNA, known as mitochondrial DNA (mtDNA), which is inherited maternally. This means that mtDNA is passed down from the mother to her offspring through the egg cells. Mitochondrial dysfunction has been linked to a variety of diseases and conditions, including neurodegenerative disorders, diabetes, and aging.
Phalloidine is not a medical term, but it is often referenced in the field of toxicology and mycology. Phalloidine is a toxin found in certain species of mushrooms, including the death cap (Amanita phalloides) and the destroying angel (Amanita virosa). It is one of the most potent and deadly toxins known to affect humans.
Phalloidine is a cyclic peptide that inhibits the function of actin, a protein involved in cell movement and division. By interfering with actin's normal functioning, phalloidine causes severe damage to the liver, kidneys, and other organs, leading to symptoms such as vomiting, diarrhea, dehydration, electrolyte imbalances, and potentially fatal organ failure.
It is important to note that phalloidine poisoning can be difficult to diagnose and treat, and it often requires prompt medical attention and supportive care to manage the symptoms and prevent long-term damage or death.
Multiple drug resistance in fungi refers to the ability of certain fungal strains or species to resist the effects of multiple antifungal agents. This occurs when these organisms develop mechanisms that prevent the drugs from interfering with their growth and survival. As a result, the drugs become less effective or even completely ineffective at treating fungal infections caused by these resistant strains or species.
Multiple drug resistance in fungi can arise due to various factors, including genetic mutations, overuse or misuse of antifungal agents, and the ability of fungi to exchange genetic material with other fungi. This makes treatment of fungal infections more challenging, as doctors may need to use higher doses of drugs or try alternative therapies that may have more side effects or be less effective.
Multiple drug resistance in fungi is a significant concern in healthcare settings, particularly for patients who are immunocompromised or have underlying medical conditions that make them more susceptible to fungal infections. It is essential to take measures to prevent the development and spread of multiple drug-resistant fungi, such as using antifungal agents appropriately, practicing good infection control practices, and conducting surveillance for resistant strains.
Sodium azide is a chemical compound with the formula NaN3. Medically, it is not used as a treatment, but it can be found in some pharmaceutical and laboratory settings. It is a white crystalline powder that is highly soluble in water and has a relatively low melting point.
Sodium azide is well known for its ability to release nitrogen gas upon decomposition, which makes it useful as a propellant in airbags and as a preservative in laboratory settings to prevent bacterial growth. However, this property also makes it highly toxic to both animals and humans if ingested or inhaled, as it can cause rapid respiratory failure due to the release of nitrogen gas in the body. Therefore, it should be handled with great care and appropriate safety measures.
Biological transport refers to the movement of molecules, ions, or solutes across biological membranes or through cells in living organisms. This process is essential for maintaining homeostasis, regulating cellular functions, and enabling communication between cells. There are two main types of biological transport: passive transport and active transport.
Passive transport does not require the input of energy and includes:
1. Diffusion: The random movement of molecules from an area of high concentration to an area of low concentration until equilibrium is reached.
2. Osmosis: The diffusion of solvent molecules (usually water) across a semi-permeable membrane from an area of lower solute concentration to an area of higher solute concentration.
3. Facilitated diffusion: The assisted passage of polar or charged substances through protein channels or carriers in the cell membrane, which increases the rate of diffusion without consuming energy.
Active transport requires the input of energy (in the form of ATP) and includes:
1. Primary active transport: The direct use of ATP to move molecules against their concentration gradient, often driven by specific transport proteins called pumps.
2. Secondary active transport: The coupling of the movement of one substance down its electrochemical gradient with the uphill transport of another substance, mediated by a shared transport protein. This process is also known as co-transport or counter-transport.
Retrograde obturation is a procedure used in endodontics, which is the branch of dentistry dealing with the dental pulp and tissues surrounding the root of a tooth. The goal of this procedure is to seal the root canal system from the bottom up, filling it with a suitable material to prevent reinfection or recontamination.
In a retrograde obturation, the clinician gains access to the apical (tip) end of the root canal by creating an opening through the tooth's crown or the surrounding bone. After carefully cleaning and shaping the apical portion of the root canal, a filling material is introduced into the space in a backward or "retrograde" direction. This process aims to create a tight seal that prevents bacteria and their byproducts from entering the root canal system and causing further infection or inflammation.
The most commonly used materials for retrograde obturation include:
1. Zinc oxide-eugenol cement (IRM, Super EBA)
2. Mineral trioxide aggregate (MTA)
3. Bioceramic sealers (i.e., Biodentine, Endosequence BC RRM Putty)
Retrograde obturation is typically performed during apical surgery or periradicular surgery when conventional root canal treatment has failed to resolve a persistent infection or inflammation in the periapical tissues.
P-glycoproteins (P-gp), also known as multidrug resistance proteins (MDR), are a type of transmembrane protein that functions as an efflux pump, actively transporting various substrates out of cells. They play a crucial role in the protection of cells against xenobiotics, including drugs, toxins, and carcinogens. P-gp is expressed in many tissues, such as the intestine, liver, kidney, and blood-brain barrier, where it helps limit the absorption and distribution of drugs and other toxic substances.
In the context of medicine and pharmacology, P-glycoproteins are particularly relevant due to their ability to confer multidrug resistance in cancer cells. Overexpression of P-gp in tumor cells can lead to reduced intracellular drug concentrations, making these cells less sensitive to chemotherapeutic agents and contributing to treatment failure. Understanding the function and regulation of P-glycoproteins is essential for developing strategies to overcome multidrug resistance in cancer therapy.
'Staining and labeling' are techniques commonly used in pathology, histology, cytology, and molecular biology to highlight or identify specific components or structures within tissues, cells, or molecules. These methods enable researchers and medical professionals to visualize and analyze the distribution, localization, and interaction of biological entities, contributing to a better understanding of diseases, cellular processes, and potential therapeutic targets.
Medical definitions for 'staining' and 'labeling' are as follows:
1. Staining: A process that involves applying dyes or stains to tissues, cells, or molecules to enhance their contrast and reveal specific structures or components. Stains can be categorized into basic stains (which highlight acidic structures) and acidic stains (which highlight basic structures). Common staining techniques include Hematoxylin and Eosin (H&E), which differentiates cell nuclei from the surrounding cytoplasm and extracellular matrix; special stains, such as PAS (Periodic Acid-Schiff) for carbohydrates or Masson's trichrome for collagen fibers; and immunostains, which use antibodies to target specific proteins.
2. Labeling: A process that involves attaching a detectable marker or tag to a molecule of interest, allowing its identification, quantification, or tracking within a biological system. Labels can be direct, where the marker is directly conjugated to the targeting molecule, or indirect, where an intermediate linker molecule is used to attach the label to the target. Common labeling techniques include fluorescent labels (such as FITC, TRITC, or Alexa Fluor), enzymatic labels (such as horseradish peroxidase or alkaline phosphatase), and radioactive labels (such as ³²P or ¹⁴C). Labeling is often used in conjunction with staining techniques to enhance the specificity and sensitivity of detection.
Together, staining and labeling provide valuable tools for medical research, diagnostics, and therapeutic development, offering insights into cellular and molecular processes that underlie health and disease.
Fluorescence is not a medical term per se, but it is widely used in the medical field, particularly in diagnostic tests, medical devices, and research. Fluorescence is a physical phenomenon where a substance absorbs light at a specific wavelength and then emits light at a longer wavelength. This process, often referred to as fluorescing, results in the emission of visible light that can be detected and measured.
In medical terms, fluorescence is used in various applications such as:
1. In-vivo imaging: Fluorescent dyes or probes are introduced into the body to highlight specific structures, cells, or molecules during imaging procedures. This technique can help doctors detect and diagnose diseases such as cancer, inflammation, or infection.
2. Microscopy: Fluorescence microscopy is a powerful tool for visualizing biological samples at the cellular and molecular level. By labeling specific proteins, nucleic acids, or other molecules with fluorescent dyes, researchers can observe their distribution, interactions, and dynamics within cells and tissues.
3. Surgical guidance: Fluorescence-guided surgery is a technique where surgeons use fluorescent markers to identify critical structures such as blood vessels, nerves, or tumors during surgical procedures. This helps ensure precise and safe surgical interventions.
4. Diagnostic tests: Fluorescence-based assays are used in various diagnostic tests to detect and quantify specific biomarkers or analytes. These assays can be performed using techniques such as enzyme-linked immunosorbent assay (ELISA), polymerase chain reaction (PCR), or flow cytometry.
In summary, fluorescence is a physical process where a substance absorbs and emits light at different wavelengths. In the medical field, this phenomenon is harnessed for various applications such as in-vivo imaging, microscopy, surgical guidance, and diagnostic tests.
Confocal microscopy is a powerful imaging technique used in medical and biological research to obtain high-resolution, contrast-rich images of thick samples. This super-resolution technology provides detailed visualization of cellular structures and processes at various depths within a specimen.
In confocal microscopy, a laser beam focused through a pinhole illuminates a small spot within the sample. The emitted fluorescence or reflected light from this spot is then collected by a detector, passing through a second pinhole that ensures only light from the focal plane reaches the detector. This process eliminates out-of-focus light, resulting in sharp images with improved contrast compared to conventional widefield microscopy.
By scanning the laser beam across the sample in a raster pattern and collecting fluorescence at each point, confocal microscopy generates optical sections of the specimen. These sections can be combined to create three-dimensional reconstructions, allowing researchers to study cellular architecture and interactions within complex tissues.
Confocal microscopy has numerous applications in medical research, including studying protein localization, tracking intracellular dynamics, analyzing cell morphology, and investigating disease mechanisms at the cellular level. Additionally, it is widely used in clinical settings for diagnostic purposes, such as analyzing skin lesions or detecting pathogens in patient samples.
Carbocyanines are a class of organic compounds that contain a polymethine chain, which is a type of carbon-based structure with alternating single and double bonds, and one or more cyanine groups. A cyanine group is a functional group consisting of a nitrogen atom connected to two carbon atoms by double bonds, with the remaining valences on the carbon atoms being satisfied by other groups.
Carbocyanines are known for their strong absorption and fluorescence properties in the visible and near-infrared regions of the electromagnetic spectrum. These properties make them useful as dyes and fluorescent labels in various applications, including biomedical research, clinical diagnostics, and material science.
In medicine, carbocyanines are sometimes used as fluorescent contrast agents for imaging purposes. They can be injected into the body and accumulate in certain tissues or organs, where they emit light when excited by a specific wavelength of light. This allows doctors to visualize the distribution of the agent and potentially detect abnormalities such as tumors or inflammation.
It is important to note that while carbocyanines have potential medical applications, they are not themselves medications or drugs. They are tools used in various medical procedures and research.
Gossypol is not typically defined in a medical context as it is not a medication or a specific medical condition. However, it is a chemical compound that can be found in the cotton plant (Gossypium species). It's a polyphenolic compound that is present in the seeds, leaves and roots of the cotton plant.
Gossypol has been studied for its potential medicinal properties, such as its anti-fertility effects, and it has also been investigated for its potential use as an anticancer agent. However, its toxicity and side effects have limited its clinical use.
It's important to note that gossypol can be toxic in high concentrations, and consuming large amounts of cottonseed or cottonseed products can lead to gossypol poisoning. Symptoms of gossypol poisoning may include nausea, vomiting, diarrhea, abdominal pain, and neurological symptoms such as weakness, dizziness, and difficulty breathing.
Flow cytometry is a medical and research technique used to measure physical and chemical characteristics of cells or particles, one cell at a time, as they flow in a fluid stream through a beam of light. The properties measured include:
* Cell size (light scatter)
* Cell internal complexity (granularity, also light scatter)
* Presence or absence of specific proteins or other molecules on the cell surface or inside the cell (using fluorescent antibodies or other fluorescent probes)
The technique is widely used in cell counting, cell sorting, protein engineering, biomarker discovery and monitoring disease progression, particularly in hematology, immunology, and cancer research.
"Energy transfer" is a general term used in the field of physics and physiology, including medical sciences, to describe the process by which energy is passed from one system, entity, or location to another. In the context of medicine, energy transfer often refers to the ways in which cells and organ systems exchange and utilize various forms of energy for proper functioning and maintenance of life.
In a more specific sense, "energy transfer" may refer to:
1. Bioenergetics: This is the study of energy flow through living organisms, including the conversion, storage, and utilization of energy in biological systems. Key processes include cellular respiration, photosynthesis, and metabolic pathways that transform energy into forms useful for growth, maintenance, and reproduction.
2. Electron transfer: In biochemistry, electrons are transferred between molecules during redox reactions, which play a crucial role in energy production and consumption within cells. Examples include the electron transport chain (ETC) in mitochondria, where high-energy electrons from NADH and FADH2 are passed along a series of protein complexes to generate an electrochemical gradient that drives ATP synthesis.
3. Heat transfer: This is the exchange of thermal energy between systems or objects due to temperature differences. In medicine, heat transfer can be relevant in understanding how body temperature is regulated and maintained, as well as in therapeutic interventions such as hyperthermia or cryotherapy.
4. Mechanical energy transfer: This refers to the transmission of mechanical force or motion from one part of the body to another. For instance, muscle contractions generate forces that are transmitted through tendons and bones to produce movement and maintain posture.
5. Radiation therapy: In oncology, ionizing radiation is used to treat cancer by transferring energy to malignant cells, causing damage to their DNA and leading to cell death or impaired function.
6. Magnetic resonance imaging (MRI): This non-invasive diagnostic technique uses magnetic fields and radio waves to excite hydrogen nuclei in the body, which then release energy as they return to their ground state. The resulting signals are used to generate detailed images of internal structures and tissues.
In summary, "energy transfer" is a broad term that encompasses various processes by which different forms of energy (thermal, mechanical, electromagnetic, etc.) are exchanged or transmitted between systems or objects in the context of medicine and healthcare.
Coloring agents, also known as food dyes or color additives, are substances that are added to foods, medications, and cosmetics to improve their appearance by giving them a specific color. These agents can be made from both synthetic and natural sources. They must be approved by regulatory agencies such as the U.S. Food and Drug Administration (FDA) before they can be used in products intended for human consumption.
Coloring agents are used for various reasons, including:
* To replace color lost during food processing or preparation
* To make foods more visually appealing
* To help consumers easily identify certain types of food
* To indicate the flavor of a product (e.g., fruit-flavored candies)
It's important to note that while coloring agents can enhance the appearance of products, they do not affect their taste or nutritional value. Some people may have allergic reactions to certain coloring agents, so it's essential to check product labels if you have any known allergies. Additionally, excessive consumption of some synthetic coloring agents has been linked to health concerns, so moderation is key.
Daunorubicin is an anthracycline antibiotic used in the treatment of various types of cancer, including leukemia, Hodgkin's lymphoma, and breast cancer. It works by intercalating with DNA and inhibiting topoisomerase II, which results in DNA damage and ultimately cell death.
The drug is administered intravenously and may cause side effects such as nausea, vomiting, hair loss, mouth sores, and damage to the heart muscle (cardiotoxicity) with long-term use. Regular monitoring of cardiac function is recommended during treatment with daunorubicin.
It's important to note that this medication should only be used under the supervision of a qualified healthcare professional, as it can have serious and potentially life-threatening consequences if not used correctly.
Fluorescence Polarization (FP) is not a medical term per se, but a technique used in medical research and diagnostics. Here's a general definition:
Fluorescence Polarization is a biophysical technique used to measure the rotational movement of molecules in solution after they have been excited by polarized light. When a fluorophore (a fluorescent molecule) absorbs light, its electrons become excited and then return to their ground state, releasing energy in the form of light. This emitted light often has different properties than the incident light, one of which can be its polarization. If the fluorophore is large or bound to a large structure, it may not rotate significantly during the time between absorption and emission, resulting in emitted light that maintains the same polarization as the excitation light. Conversely, if the fluorophore is small or unbound, it will rotate rapidly during this period, and the emitted light will be depolarized. By measuring the degree of polarization of the emitted light, researchers can gain information about the size, shape, and mobility of the fluorophore and the molecules to which it is attached. This technique is widely used in various fields including life sciences, biochemistry, and diagnostics.
ATP-binding cassette (ABC) transporters are a family of membrane proteins that utilize the energy from ATP hydrolysis to transport various substrates across extra- and intracellular membranes. These transporters play crucial roles in several biological processes, including detoxification, drug resistance, nutrient uptake, and regulation of cellular cholesterol homeostasis.
The structure of ABC transporters consists of two nucleotide-binding domains (NBDs) that bind and hydrolyze ATP, and two transmembrane domains (TMDs) that form the substrate-translocation pathway. The NBDs are typically located adjacent to each other in the cytoplasm, while the TMDs can be either integral membrane domains or separate structures associated with the membrane.
The human genome encodes 48 distinct ABC transporters, which are classified into seven subfamilies (ABCA-ABCG) based on their sequence similarity and domain organization. Some well-known examples of ABC transporters include P-glycoprotein (ABCB1), multidrug resistance protein 1 (ABCC1), and breast cancer resistance protein (ABCG2).
Dysregulation or mutations in ABC transporters have been implicated in various diseases, such as cystic fibrosis, neurological disorders, and cancer. In cancer, overexpression of certain ABC transporters can contribute to drug resistance by actively effluxing chemotherapeutic agents from cancer cells, making them less susceptible to treatment.
Cyclosporins are a group of cyclic undecapeptides that have immunosuppressive properties. The most well-known and widely used cyclosporin is cyclosporine A, which is commonly used in organ transplantation to prevent rejection. It works by inhibiting the activation of T-cells, a type of white blood cell that plays a central role in the immune response. By suppressing the activity of T-cells, cyclosporine A reduces the risk of an immune response against the transplanted organ.
Cyclosporins are also used in the treatment of autoimmune diseases, such as rheumatoid arthritis and psoriasis, where they help to reduce inflammation and prevent damage to tissues. Like all immunosuppressive drugs, cyclosporins can increase the risk of infection and cancer, so they must be used with caution and under close medical supervision.
Multidrug Resistance-Associated Proteins (MRPs) are a subfamily of ATP-binding cassette (ABC) transporter proteins that play a crucial role in the efflux of various substrates, including drugs and organic anions, out of cells. They are located in the plasma membrane of many cell types, including epithelial cells in the liver, intestine, kidney, and blood-brain barrier.
MRPs are known to transport a wide range of molecules, such as glutathione conjugates, bilirubin, bile acids, and various clinical drugs. One of the most well-known MRPs is MRP1 (ABCC1), which was initially identified in drug-resistant tumor cells. MRP1 can confer resistance to chemotherapeutic agents by actively pumping them out of cancer cells, thereby reducing their intracellular concentration and effectiveness.
The activity of MRPs can have significant implications for the pharmacokinetics and pharmacodynamics of drugs, as they can affect drug absorption, distribution, metabolism, and excretion (ADME). Understanding the function and regulation of MRPs is essential for developing strategies to overcome multidrug resistance in cancer therapy and optimizing drug dosing regimens in various clinical settings.