The short version of blood-brain barrier fits in a sentence. The long version — which is the one that helps — is below.
This page was last updated on 2025-09-28 and is reviewed periodically as new material appears.
Proposed mechanisms centre on the GABAergic system. Animal and tissue studies report changes in GABA-A receptor expression and reduced activity of GABA transaminase, the enzyme that degrades GABA. Effects on monoamine turnover, including serotonin and dopamine pathways, are also described, and a separate line of work links the peptide to increased expression of brain-derived neurotrophic factor in hippocampal tissue. Most of these findings come from rodent models and cell preparations. How the individual observations combine into a single coherent mode of action is not settled.
Pharmacokinetic data are sparse and largely derived from animal work. After intranasal administration the peptide appears in plasma within minutes, and reported half-lives are short, on the order of minutes to tens of minutes. Degradation proceeds through ordinary proteolytic cleavage into constituent amino acids and smaller fragments. Direct evidence that intact Selank reaches brain tissue in meaningful amounts is limited, and the extent of blood-brain barrier penetration is debated. Some authors argue that fragments, not the parent peptide, carry much of the observed activity.
Published clinical work is concentrated in Russian-language journals and generally involves small samples without independent replication. Systematic reviews in English note the shortage of randomised, placebo-controlled trials and the difficulty of verifying methods from translated reports. Outcome measures vary between studies, which complicates pooling of results. Interest in the compound as a cognitive or anxiolytic agent therefore rests on a thinner evidence base than the volume of citations suggests. Replication in well-powered trials with preregistered endpoints would be needed before firm conclusions about efficacy can be drawn.
Selank is a synthetic heptapeptide with the sequence Thr-Lys-Pro-Arg-Pro-Gly-Pro, frequently abbreviated as TKPRPGP. It was designed as a structural analogue of tuftsin, a naturally occurring tetrapeptide released by enzymatic cleavage of the immunoglobulin heavy chain. The two additional proline residues at the C-terminal end extend the parent chain and change how the molecule behaves in solution. The free peptide has a calculated molecular mass of approximately 751.9 g/mol and is generally supplied as a lyophilised white to off-white powder.
Development work on the compound began in the 1980s and 1990s at the Institute of Molecular Genetics in Moscow, within the same research programme that produced the peptide Semax. Early investigators sought a tuftsin derivative with improved resistance to enzymatic breakdown and with activity in the central nervous system after peripheral administration. Most of the primary literature from this period was published in Russian, a factor that still shapes how easily the findings can be checked by outside groups.
| Property | Value | Notes |
|---|---|---|
| Primary route studied | Intranasal | Also examined parenterally in animal work |
| Reported plasma half-life | Minutes to tens of minutes | Values vary widely between reports |
| Main model systems | Rodent behavioural and cell assays | Human trials are few and small |
| Principal proposed targets | GABA-A receptor, GABA transaminase | Monoamine and neurotrophic pathways also reported |
| Evidence grade | Preliminary | Limited independent replication |
Selank is a synthetic heptapeptide developed in Russia during the 1990s. Researchers at the Institute of Molecular Genetics of the Russian Academy of Sciences designed it as a stabilized analog of tuftsin, a naturally occurring immunomodulatory tetrapeptide. The compound has been studied primarily for its reported anxiolytic and nootropic effects. It remains largely unknown in Western pharmacology and is not approved as a medicine by major regulators such as the FDA or the EMA.
The primary structure of Selank is Thr-Lys-Pro-Arg-Pro-Gly-Pro, corresponding to the molecular formula C33H57N11O9 and a monoisotopic mass of roughly 751.9 daltons. The N-terminal threonine and the arginine residue in the fourth position are shared with tuftsin, which carries the sequence Thr-Lys-Pro-Arg. The three additional residues at the C-terminus, Pro-Gly-Pro, extend the chain and are associated with greater resistance to enzymatic degradation. This extension also separates Selank from the shorter parent peptide.
Lyophilized Selank, the dry powder form, is generally stored frozen at minus 20 degrees Celsius or colder for long-term keeping. The solid is hygroscopic and should stay sealed, dry, and protected from light. Once dissolved, the peptide is less stable and is usually held refrigerated at 2 to 8 degrees Celsius for short periods. Repeated freezing and thawing is avoided because it can promote aggregation and loss of activity. Buffers and pH choice also affect how long a solution remains usable.
Solubility behavior is a practical concern for handling. Selank dissolves readily in water and in common aqueous buffers, which simplifies preparation of working solutions. The choice of solvent, ionic strength, and pH can influence aggregation over time, particularly at higher concentrations. Aqueous solutions are typically sterile-filtered before use. Because stability depends on several variables, storage and handling notes should be treated as general guidance rather than fixed rules, and specific values are best confirmed against a certificate of analysis for each batch.
Measuring peptide exposure inside the brain is technically difficult. Selank is degraded rapidly in plasma, and assays must separate intact peptide from fragments, which favors targeted mass spectrometry over immunoassays alone. Reported half-lives are short, on the order of minutes, so effects observed hours later are attributed to downstream signaling rather than to the parent compound. Blood-brain barrier permeability is debated and rarely quantified directly. Gaps include absent dose-response characterization, inconsistent reporting of purity, and almost no pharmacokinetic data from human participants.
Selank is studied chiefly as an animal-model anxiolytic with proposed secondary effects on memory and immune signaling. Reported mechanisms include modulation of the GABA-A receptor complex, inhibition of enkephalin-degrading enzymes, and shifts in monoamine turnover within limbic structures. Some experiments describe increased expression of brain-derived neurotrophic factor in the hippocampus after repeated dosing. No single molecular target has been confirmed, and the peptide does not bind any receptor with the selectivity typical of a conventional small-molecule drug. Mechanism therefore remains a set of hypotheses rather than an established pathway.
Laboratory work relies on standard behavioral paradigms. Rodents are tested in the elevated plus maze, open field, and passive avoidance tasks, with outcomes compared against diazepam or vehicle controls. Intranasal dosing is used most often because it bypasses first-pass metabolism, though intraperitoneal and intravenous routes also appear in published protocols. Biochemical endpoints include tissue BDNF concentrations, cytokine levels, and monoamine metabolites. Human data are limited to small Russian trials reporting reduced anxiety scores; most were not prospectively registered, and few employed independent outcome assessment.
The most important food sources are commodities widely consumed in large quantities such as fruit and vegetables, green tea, black tea, red wine, coffee, chocolate, olives, and extra virgin olive oil. Herbs and spices, nuts and algae are also potentially significant for supplying certain polyphenols. Some polyphenols are specific to particular food (flavanones in citrus fruit, isoflavones in soya, phloridzin in apples); whereas others, such as quercetin, are found in all plant products such as fruit, vegetables, cereals, leguminous plants, tea, and wine. Some polyphenols, such as isoflavones, proanthocyanidins, and ellagitannins, may have antinutrient properties interfering with the absorption of essential nutrients – especially iron and other metallic minerals – by binding to digestive enzymes, particularly in ruminants. In a comparison of cooking methods, phenolic and carotenoid levels in vegetables were retained better by steaming compared to frying. Polyphenols in wine, beer and various nonalcoholic juice beverages can be removed using finings, substances that are usually added at or near the completion of the processing of brewing.
== Structure == In humans, granzyme B is encoded by GZMB on chromosome 14q11.2, which is 3.2kb long and consists of 5 exons. It is one of the most abundant granzymes of which there are 5 in humans and 10 in mice. Granzyme B is thought to have evolved from a granzyme H related precursor and is more effective at lower concentrations than the other granzymes. The enzyme is initially in an inactive precursor zymogen form, with an additional amino terminal peptide sequence. This sequence can be cleaved by cathepsin C, removing 2 amino acids. Cathepsin H has also been reported to activate granzyme B. Granzyme B's structure consists of two six-stranded β sheets with three trans domain segments. In the granules of cytotoxic lymphocytes the enzyme can exist in two glycosylated forms. The high mannose form weighs 32kDa and the complex form, 35kDa. Granzyme B contains the catalytic triad histidine-aspartic acid-serine in its active site and preferentially cleaves after an aspartic acid residue situated in the P1 position. The aspartic acid residue to be cleaved associates with an arginine residue in the enzyme's binding pocket. Granzyme B is active at a neutral pH and is therefore inactive in the acidic CTL granules. The enzyme is also rendered inactive when bound by serglycin in the granules to avoid apoptosis triggering inside the cytotoxic T cells themselves.
=== Reception === The Bush presidency has been ranked as below-average in surveys of presidential scholars published in the late 2000s and 2010s. A 2010 Siena Research Institute survey of the opinions of historians, political scientists, and presidential scholars ranked him 39th out of 43 presidents. The survey respondents gave Bush low ratings on his handling of the economy, communication, ability to compromise, foreign policy, and intelligence. Bush said in 2013, "Ultimately history will judge the decisions I made, and I won't be around because it will take time for the objective historians to show up. So I am pretty comfortable with it. I did what I did." C-SPAN's 2021 survey of historians ranked Bush as the 29th-best president; Bush had initially been ranked 36th in 2009. Among the public, his reputation has improved in the U.S. since his presidency ended in 2009. In 2012, Gallup reported that "Americans still rate George W. Bush among the worst presidents, though their views have become more positive in the three years since he left office." A poll conducted in 2013 marked the first time recorded by Gallup that his ratings were more positive than negative, with 49 percent viewing him favorably compared to 46 percent unfavorably. Other pollsters have noted similar trends of slight improvement in Bush's personal favorability since the end of his presidency. In April 2013, Bush's approval rating stood at 47 percent approval and 50 percent disapproval in a poll jointly conducted for The Washington Post and ABC, his highest approval rating since December 2005.
Sources: en.wikipedia.org
==== Vitatron ==== Vitatron is a Netherlands-based European subsidiary of Medtronic. It is focused on development and manufacturing of cardiac pacing technology. Once an independently operating Dutch medical company, it was acquired by Medtronic in 1986. Vitatron pacemakers are interrogated and programmed by Medtronic Carelink Model 2090 Programmer for Medtronic and Vitatron Devices, using a separate interface.
=== Breastfeeding === While only small amounts of lithium are transmitted to the infant in breastmilk, there is limited data on the safety of breastfeeding while on lithium. Medical evaluation and monitoring of infants consuming breastmilk during maternal prescription may be indicated.
== Mechanism of action == Melanotan II acts as a non-selective agonist of the melanocortin receptors MC1, MC3, MC4, and MC5. Melanotan II produces melanogenesis by activation of the MC1 receptor, whereas its clinically documented sexual effects are thought to be related to its ability to activate the MC4 receptor (though the MC3 is thought to also possibly be involved). Melanotan II is partly metabolised into Bremelanotide, a medication used to treat low sexual desire. Other effects of melanotan II, mostly regarded as adverse effects, include flushing, nausea, vomiting, stretching, yawning, and loss of appetite (the last via activation of MC4).
Sources: en.wikipedia.org
In blood serum, the content of nitrogenous substances such as urea and creatinine (uremia or azotemia) and phosphate (hyperphosphatemia). The increased phosphate concentration is the result of the reduced glomerular filtration rate. Among other things, fibroblast growth factor 23 (FGF-23) is involved here, which is more sensitive than the phosphate level in the event of an incipient disorder. The potassium content is usually reduced (hypokalemia), but can also be increased—the reverse is true for the sodium content. If the cause of the kidney disease lies in the renal corpuscles, albumin deficiency (hypalbuminemia) and excess cholesterol (hypercholesterolemia) also occur. The determination of cystatin C is not evaluated for cats, this protein can also be elevated in cats with hyperthyroidism or with glucocorticoids and drop sharply for several hours after food intake. Recent studies suggest that symmetric dimethylarginine (SDMA) is a suitable marker for renal function in cats. The SDMA concentration in serum shows close correlations with the glomerular filtration rate and the creatinine concentration. It can already detect a 40% loss of kidney function, i.e. before there is an increase in creatinine in the blood. The most sensitive method of kidney function diagnostics is the direct determination of the glomerular filtration rate via the clearance, which is already reduced in chronic kidney disease before azotemia occurs. Various substances have been evaluated for cats, the most practical being creatinine and iohexol.
The left corridor had a beautiful mural showing a monk transmitting the teachings of the Buddha to a kneeling royal family, whether the mural in front of it on the external wall was entirely gone. Similarities have been noted between the paintings of the Cave of the Painters and those of Dilberjin Tepe and Penjikent of the 5th–6th centuries.
The discovery of the element is credited to the German chemist Martin Heinrich Klaproth. While he was working in his experimental laboratory in Berlin in 1789, Klaproth was able to precipitate a yellow compound (likely sodium diuranate) by dissolving pitchblende in nitric acid and neutralizing the solution with sodium hydroxide. Klaproth assumed the yellow substance was the oxide of a yet-undiscovered element and heated it with charcoal to obtain a black powder, which he thought was the newly discovered metal itself (in fact, that powder was an oxide of uranium). He named the newly discovered element "Uranit" after the planet Uranus (named after the primordial Greek god of the sky), which had been discovered eight years earlier by William Herschel. He later renamed it "Uranium" to conform to the naming standard. In 1841, Eugène-Melchior Péligot, Professor of Analytical Chemistry at the Conservatoire National des Arts et Métiers (Central School of Arts and Manufactures) in Paris, isolated the first sample of uranium metal by heating uranium tetrachloride with potassium.
=== STC1 === STC1 was discovered in 1995 from human kidney. It was demonstrated that human kidney extract produced the same calcium inhibitory action when injected in a fish. The gene that produce STC1, STC1 is located in the short arm of human chromosome 8 (position p21.2). STC1 mRNA is formed in heart, lung, liver, adrenal gland, prostate, and ovary, indicating that these are the sites of synthesis. Ovary contains the highest level of STC1 mRNA. Fish stanniocalcin and mammalian STC1 are closely related, and are about 50% similar in their structure. They are both responsible for calcium and phosphate balance. In mammals the predominant function of STC1 is to activate phosphate reabsorption in the small intestine and proximal tubules of the kidney.
Sources: en.wikipedia.org
Reports describe modulation of GABA signalling, changes in monoamine turnover and effects on neurotrophic factor expression. These observations come mainly from animal and cell studies. A single unifying mechanism has not been demonstrated.
The peptide enters plasma rapidly and is broken down by ordinary proteases into amino acids and shorter fragments. Reported half-lives are short. Whether meaningful amounts of the intact molecule reach the brain is an open question.
Most clinical reports are small, published in Russian and not independently replicated. English-language reviews highlight the absence of large randomised trials. Conclusions about efficacy should be treated as provisional.
The sequence is Thr-Lys-Pro-Arg-Pro-Gly-Pro, commonly written as TKPRPGP. It shares the first four residues with tuftsin and carries three prolines in the chain. The proline-rich tail is the main structural feature that separates it from the parent tetrapeptide.