This is a working overview of neurotrophic signaling, written for readers who want more than a one-paragraph summary but less than a textbook.
Reviewed 2026-03-16. Anything still debated is marked as such rather than presented as settled.
Pharmacokinetic accounts emphasize rapid breakdown. After intravenous dosing the intact peptide disappears from blood within minutes, and nasal delivery produces low but measurable concentrations. Metabolites rather than the parent molecule may account for part of the observed activity, although the relative contribution is unresolved. Dosing in the literature varies widely and no optimal schedule has been agreed. These gaps are regularly cited as a reason the findings have not produced broad clinical adoption beyond the original research setting.
Proposed mechanisms center on neurotrophic signaling rather than on classical melanocortin receptor activation. Rodent experiments have reported shifts in the expression of brain-derived neurotrophic factor and nerve growth factor after administration, together with changes in the associated receptor systems. Several authors argue that the peptide acts largely through its degradation products and their interaction with peptidergic pathways, but this remains a hypothesis rather than a settled finding. No single molecular target has been identified in a way that the field broadly accepts.
Clinical evidence consists largely of small trials with modest sample sizes, often without independent replication. Reported endpoints include cognitive scores, recovery after stroke, and visual function, but study designs vary widely and few trials meet contemporary reporting standards. Systematic reviewers have noted a high risk of bias in several of these reports. No large multicenter trial conducted outside Russia has been published. The compound is therefore best described as investigational in most jurisdictions, with its clinical role still unresolved.
Semax is a synthetic heptapeptide with the sequence Met-Glu-His-Phe-Pro-Gly-Pro. Its chain combines the first seven residues of corticotropin with a C-terminal proline-glycine-proline extension, a modification intended to slow enzymatic breakdown. The free peptide has a molecular mass near 813.9 daltons. It belongs to the class of ACTH-derived fragments studied for central nervous system activity rather than for adrenal steroid stimulation. This structural relationship to a natural hormone fragment is the usual starting point for describing the compound in the literature.
Development took place during the 1980s at institutes of the Russian Academy of Sciences, where peptide fragments of ACTH were screened for cognitive and neuroprotective effects. The compound received regulatory approval in Russia as a nasal preparation, marketed for conditions such as ischemic stroke, transient ischemic attacks, and optic nerve disorders. Registration in other countries has not followed. Most published clinical reports originate from a small number of Russian research groups, and independent replication outside that setting remains limited. The regulatory status therefore differs sharply between Russia and the rest of the world.
| Property | Value | Notes |
|---|---|---|
| Primary research models | Rodent studies | Largest share of published data |
| Reported markers | BDNF and NGF expression | Measured mainly in animal tissue |
| Common administration | Intranasal | Matches the registered formulation |
| Blood residence time | Minutes | Rapid enzymatic degradation |
| Evidence quality | Small trials, limited replication | Noted repeatedly in reviews |
Identity and purity are established with standard peptide methods. Reversed-phase HPLC with ultraviolet detection near 214 nm resolves the parent peak from deletion and truncation byproducts, and reports typically quote a main-peak percentage. Mass spectrometry by electrospray or MALDI-TOF confirms the expected molecular mass, while amino acid analysis or peptide mapping can verify composition when the sequence itself is in question. A certificate of analysis that pairs a chromatogram with a mass spectrum is more informative than a purity figure alone. Counter-ion content and residual solvents are separate specifications and are frequently omitted.
Semax is normally supplied as a lyophilized powder, and that form is the most stable. Suppliers commonly recommend storage at -20 °C in a desiccated container protected from light, with short-term handling at room temperature limited to weighing and transfer. Powder that has absorbed moisture degrades faster, so vials should be warmed to ambient temperature before opening to prevent condensation on the contents. Hygroscopic behavior is typical of short hydrophilic peptides, and humidity control matters more than temperature alone for long-term retention.
Once dissolved, the peptide is considerably less stable than the solid. Aqueous solutions are usually prepared at neutral to slightly acidic pH, filtered, and divided into single-use aliquots before freezing. Repeated freeze-thaw cycles are a common cause of avoidable loss and are best prevented by never refreezing a thawed aliquot. Adsorption to plastic and glass surfaces can lower the measured concentration of dilute solutions, particularly below roughly 0.1 mg/mL. Buffer choice, salt content, and container material all influence how much peptide remains detectable after storage.
Regulatory status differs sharply between jurisdictions. In Russia the peptide is registered as a prescription nasal preparation, while agencies such as the United States Food and Drug Administration have not approved it for any indication. Products sold elsewhere are typically labeled for laboratory research only, and such labels shift responsibility for safe handling to the purchaser. Because the same name covers pharmaceutical-grade nasal drops and bulk research powder, identity and purity documentation becomes the main practical concern when comparing sources.
Semax is a synthetic seven-amino-acid peptide whose sequence extends the ACTH(4-10) fragment with a C-terminal proline-glycine-proline tripeptide. The commonly cited sequence is Met-Glu-His-Phe-Pro-Gly-Pro, giving a molecular formula near C37H51N9O10S and a molecular weight close to 813.9 g/mol. It belongs to the broader class of synthetic ACTH fragments studied for central nervous system effects rather than for adrenal steroid stimulation. In practice the material appears as a lyophilized white powder for laboratory work or as a dilute saline solution in clinical settings.
Development is attributed to researchers at the Institute of Molecular Genetics in Moscow during the early 1980s, building on earlier Soviet work with ACTH fragments. Russian regulatory approval followed for intranasal use, and the compound has remained commercially available there for decades. Most published human data originate from Russian and, later, some Eastern European clinical reports, which are not always accessible in English translation. Outside that region the material is generally handled as a research chemical rather than a licensed medicine.
常规纯度与身份确认依赖反相高效液相色谱，并辅以质谱测定分子量。氨基酸组成分析可用于验证序列构成，肽图分析则能进一步定位修饰或降解产物。杂质谱通常关注缺失序列肽、截短片段和氧化产物。不同方法的检出限并不相同，因此各实验室报告的纯度数值不宜直接横向比较。
多数实验室与市售的 Semax 以冻干粉形式提供。冻干粉通常建议保存在 -20 °C 或更低温度下，同时避免光照与反复升温。短期运输有时采用冷藏条件，但长期保存仍以冷冻为主。分包操作应尽量减少开盖次数，以降低吸湿和微生物污染的风险。开封后若未一次用完，建议在干燥环境中密封并尽快放回低温储存。
溶液状态的稳定性明显低于冻干粉。肽类在水溶液中可能经历水解、氧化与聚集，其中甲硫氨酸和天冬酰胺等残基常是敏感位点。Semax 含有甲硫氨酸，因此氧化风险相对突出。工作液一般主张现配现用，或冷藏并在数日内用尽。缓冲液种类、pH 和离子强度都会影响降解速率，而关于最佳条件的公开数据并不统一。
This tissue may be further divided into two components, the actual fatty layer, or panniculus adiposus, and a deeper vestigial layer of muscle, the panniculus carnosus. The main cellular component of this tissue is the adipocyte, or fat cell. The structure of this tissue is composed of septal (i.e. linear strands) and lobular compartments, which differ in microscopic appearance. Functionally, the subcutaneous fat insulates the body, absorbs trauma, and serves as a reserve energy source. Conditions of the human integumentary system constitute a broad spectrum of diseases, also known as dermatoses, as well as many nonpathologic states (like, in certain circumstances, melanonychia and racquet nails). While only a small number of skin diseases account for most visits to the physician, thousands of skin conditions have been described. Classification of these conditions often presents many nosological challenges, since underlying etiologies and pathogenetics are often not known. Therefore, most current textbooks present a classification based on location (for example, conditions of the mucous membrane), morphology (chronic blistering conditions), etiology (skin conditions resulting from physical factors), and so on.
== Applications == There is almost no use for any isotope of einsteinium outside basic scientific research aiming at production of higher transuranium elements and superheavy elements. In 1955, mendelevium was synthesized by irradiating a target consisting of about 109 atoms of 253Es in the 60-inch cyclotron at Berkeley Laboratory. The resulting 253Es(α,n)256Md reaction yielded 17 atoms of the new element with the atomic number of 101. The rare isotope 254Es is favored for production of superheavy elements due to its large mass, relatively long half-life of 270 days, and availability in significant amounts of several micrograms. Hence 254Es was used as a target in the attempted synthesis of ununennium (element 119) in 1985 by bombarding it with calcium-48 ions at the superHILAC linear particle accelerator at Berkeley, California. No atoms were identified, setting an upper limit for the cross section of this reaction at 300 nanobarns.
== Cultural Award of the State of Hesse (2009) == In 2009, following a temporary revocation of the award, Kermani received the Hesse Cultural Award — along with Cardinal Karl Lehmann; the former president of the Church of Hesse-Nassau; Peter Steinacker; and the vice president of the Central Council of Jews, Salomon Korn. That year's ceremony was held under the theme of interreligious tolerance. The prize was offered to Kermani on March 20, 2009, after the originally intended recipient, Fuat Sezgin, had declined to accept it on the grounds that his co-recipient, Salomon Korn, supported Israel's military actions. On May 13, 2009, Kermani learned that the award intended for him had been revoked. He went on, however, to describe how this view had been shaken by what he described as the aesthetic experience: "For the first time, I thought: I — not just 'one' — I could believe in a cross." On April 24, 2009, Lehmann stated in a letter to Hesse's Minister President Roland Koch that Lehmann "cannot accept the award under these circumstances". Commentators described Lehmann's tone as "subtly ... defamatory", "smug", "mean-spirited", and "condescending"; Kermani, too, found it "defamatory". In the end, after a conversation with Kermani, Lehmann and Steinacker decided to accept the award jointly. The award was ultimately presented to the four laureates on November 26, 2009. At the ceremony, Minister President Koch apologized to Kermani. Kermani donated his prize money to Franz Meurer, the pastor of the Catholic parish of St. Theodor in Cologne-Vingst.
== History == It was founded in 1973, after the United States Department of Education pressured the American Society for Clinical Pathology(ASCP) to disband their Board of Schools (BOS) following monopolization concerns. At the time of its founding, there were seven categories of laboratory personnel: Clinical Laboratory Assistant (CLA), Medical Laboratory Technician (MLT), Medical Technologist (MT), Cytotechnologist (CT), and Histotechnologist (HT). In 2023, there was an effort to standardize program nomenclature which did not pass.
The achievement of synthesizing ribonuclease A (with Bernd Gutte) was all the more significant in that it demonstrated that the linear sequence of amino acids joined in peptide bonds determined directly the protein tertiary structure, that is, information coded in one dimension can directly determine the three-dimensional structure of a molecule. SPPS has been expanded to include solid phase synthesis of nucleotides and saccharides.
Sources: en.wikipedia.org
=== Sexual dysfunction === SSRIs can cause various types of sexual dysfunction such as anorgasmia, erectile dysfunction, diminished libido, genital numbness, and sexual anhedonia (pleasureless orgasm). Sexual problems are common with SSRIs. Poor sexual function is one of the most common reasons people stop the medication. The mechanism by which SSRIs may cause sexual side effects is not well understood as of 2021. The range of possible mechanisms includes (1) nonspecific neurological effects (e.g., sedation) that globally impair behavior including sexual function; (2) specific effects on brain systems mediating sexual function; (3) specific effects on peripheral tissues and organs, such as the penis, that mediate sexual function; and (4) direct or indirect effects on hormones mediating sexual function. Management strategies include: for erectile dysfunction the addition of a PDE5 inhibitor such as sildenafil; for decreased libido, possibly adding or switching to bupropion; and for overall sexual dysfunction, switching to nefazodone. Buspirone is sometimes used off-label to reduce sexual dysfunction associated with the use of SSRIs. A number of non-SSRI drugs are not associated with sexual side effects (such as bupropion, mirtazapine, tianeptine, agomelatine, tranylcypromine, and moclobemide). Several studies have suggested that SSRIs may adversely affect semen quality. While trazodone (an antidepressant with alpha adrenergic receptor blockade) is a notorious cause of priapism, cases of priapism have also been reported with certain SSRIs (e.g., fluoxetine, citalopram).
Before the widespread use of a vaccine against measles, rates of disease were so high that infection was felt to be "as inevitable as death and taxes." Reported cases of measles in the United States fell from hundreds of thousands to tens of thousands per year following introduction of the vaccine in 1963. Increasing uptake of the vaccine following outbreaks in 1971, and 1977, brought this down to thousands of cases per year in the 1980s. An outbreak of almost 30,000 cases in 1990 led to a renewed push for vaccination and the addition of a second vaccine to the recommended schedule. Fewer than 200 cases have been reported in the US each year between 1997 and 2013, and the disease is no longer considered endemic there. The benefit of measles vaccination in preventing illness, disability, and death has been well documented. The first 20 years of licensed measles vaccination in the US prevented an estimated 52 million cases of the disease, 17,400 cases of intellectual disability, and 5,200 deaths. During 1999–2004, a strategy led by the World Health Organization and UNICEF led to improvements in measles vaccination coverage that averted an estimated 1.4 million measles deaths worldwide. Between 2000 and 2018, measles vaccination resulted in a 73% decrease in deaths from the disease. Measles is common in many areas of the world. Although it was declared eliminated from the US in 2000, high rates of vaccination and good communication with people who refuse vaccination are needed to prevent outbreaks and sustain the elimination of measles in the US.
In addition, a very thorny issue was that of "replacements", a compensation that Peru would make to Colombian troops for the casualties suffered by them during the war, by exchanging Peruvian citizens and expatriating them to Gran Colombia, exorbitant and inhuman requirement, given that the war had already ended. Given this, Bolívar demobilized most of the Peruvian units (about five thousand who replaced the Gran Colombian casualties) and after the capitulation of Callao, presented on February 10, 1826, the demand to send 6,000 Peruvian recruits to serve Venezuela, sending the first contingents in July, probably no more than 3,000, officially to reinforce the defenses against a possible French invasion (Cien Mil Hijos de San Luis) but in reality it was to confront General Páez, who had started La Cosiata (a separatist movement in Venezuela) and also to demilitarize Peru so that it is not a future threat to its continental projects in the Patria Grande. The troops sent there, due to the distance and lack of knowledge of the language (the majority were indigenous who barely knew Spanish) made desertion or mutiny difficult, many of those sent dying due to the weather and tropical diseases. It is known that some survivors were repatriated of New Granada and Venezuela in 1852 and 1857 respectively. Due to the lifelong and authoritarian constitutions promulgated for Peru and Bolivia, the Liberator would be accused of using his armies to impose political systems, in a republican imperialism, rather than making countries independent.
Constipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation. Severe constipation includes obstipation (failure to pass stools or gas) and fecal impaction, which can progress to bowel obstruction and become life-threatening.
=== Pharmacokinetics === Nicomorphine is rapidly metabolized when administered by the I.V. route, having a half-life of 3 minutes, into morphine and 6-nicotinoylmorphine, the secondary active metabolite. Half lives of the metabolites were 3–15 minutes for the nicotinoyl metabolite, and 135–190 minutes for morphine. Via the epidural route, a much slower release from epidural space occurs and nicomorphine remains detectable for 1.5 hours or so, and has a longer effect of 18.2 +/- 10.1 hours due to slower release of the active metabolites, morphine and 6-nicotinoylmorphine. Half lives for those compounds is listed in the IV route. Pharmacokinetics via the rectal route differ, and change metabolism. Eight minutes after administration, morphine appeared rapidly, and had a half life of 1.48 +/- 0.48h. This was in turn metabolized to morphine-3- and morphine-6-glucoranides after another 12 minutes, which had similar half-lives to one-another, at about 2.8h. No 6-mononicotinoylmorphine was found, and bioavailability of morphine and metabolic actives was 88%. No remaining nicomorphine was found in urine.
Sources: en.wikipedia.org
Different vaccines have different shipping and handling requirements. For example, the Pfizer-BioNTech COVID‑19 vaccine must be shipped and stored between −80 and −60 °C (−112 and −76 °F), must be used within five days of thawing, and has a minimum order of 975 doses, making it unlikely to be rolled out in settings other than large, well-equipped hospitals. The Moderna vaccine vials require storage above −40 °C (−40 °F) and between −25 and −15 °C (−13 and 5 °F). Once refrigerated, the Moderna vaccine can be kept between 2 and 8 °C (36 and 46 °F) for up to 30 days. Vaccines (and adjuvants) are inherently unstable during temperature changes, requiring cold chain management throughout the entire supply chain, typically at temperatures of 2–8 °C (36–46 °F). Because COVID‑19 vaccine technologies are varied among several novel technologies, there are new challenges for cold chain management, with some vaccines that are stable while frozen but liable to heat, while others should not be frozen at all, and some are stable across temperatures. Failure to maintain cold chain temperature stability results in damage that can reduce or even eliminate vaccine efficacy. Sinopharm and Sinovac's vaccines are examples of inactivated vaccines which can be transported using existing cold chain systems at 2–8 °C (36–46 °F). modRNA vaccine technologies in development may be more difficult to manufacture at scale and control degradation, requiring ultracold storage and transport.
=== Tumblr === There exists a large population of self-identified mentally ill users on Tumblr, where the ability to post more unfiltered content led to individuals arguably sensationalizing and glamorizing mental illnesses and suicide. A thesis on Tumblr poetry explains how "the site serves as both a place of relief for people with mental health disorders, or even just every day growing pains, but it can also act as an enabling source for users who use the site as an echo chamber for their own problematic coping mechanisms, implying a groupthink problem that can exist in this kind of digital space." Tumblr staff attempted to prevent the use of their platform for romanticizing mental illness by changing their policies in 2012 to prohibit content actively promoting or depicting self harm and showing Public Service Announcements instead of results when users search keywords related to self-harm, such as "proana," "thinspo," "thinspiration," "purge," "bulimia," "anorexic," and more.
There are two recorded instances of the parasitic cookiecutter shark targeting white sharks off Guadalupe, though the scarcity of such records suggests white sharks are not a primary food source for them. As many as 116 parasite species infest white sharks, including copepod crustaceans—such as Nesippus orientalis, Nemesis lamna, and Dinemoura latifolia—which attach to the skin, fins, mouth, and gills. The white shark is the primary host of two species of tapeworms from the genus Clistobothrium; Clistobothrium carcharodoni and Clistobothrium tumidum. The former is believed to be transmitted to white sharks through the consumption of infected cetacean prey, while the transmission source of C. tumidum is unknown. The intensity of C. carcharodoni infestations can be remarkably high; in one documented case, as many as 2,533 specimens were recovered from the spiral valve of a single individual.
Plastic (high-density polyethylene) Composite: steel and plastic Carbon steel Stainless steel (304 and 316/316L SS grades) Some IBC engineering models are foldable (collapsible) for space-saving breakdown following use.
=== Taste disturbances === Some raw pine nuts can cause pine mouth syndrome, a taste disturbance lasting from a few days to a few weeks after consumption. A bitter, metallic, unpleasant taste is reported. There are no known lasting effects, with the United States Food and Drug Administration reporting that there are "no apparent adverse clinical side effects". Raw nuts from Pinus armandii, mainly in China, may be the cause of the problem. Metallic taste disturbance is typically reported 1–3 days after ingestion, being worse on day two and typically lasting up to two weeks. Cases are self-limited and resolve without treatment.
Sources: en.wikipedia.org
The main proposal is modulation of neurotrophic factors such as brain-derived neurotrophic factor, supported largely by animal experiments. Receptor-level targets have not been firmly established. Most reviews describe the mechanism as only partially characterized.
The compound is registered as a medicine in Russia, so clinical work has concentrated there. Trials elsewhere are few and generally small. This geographic concentration is a recognized limitation in evidence reviews.
Some fraction may reach the central nervous system through olfactory pathways, and this is often cited as the rationale for the nasal route. The size of that fraction in humans is not well quantified. Blood concentrations after nasal dosing are low, which complicates measurement.
Semax is a synthetic seven-amino-acid peptide derived from a fragment of corticotropin. It is used in Russia as a nasal preparation, while elsewhere it is studied as a research compound. It is not approved as a medicine in most countries.