freeze-thaw is one of those subjects where the details matter more than the headlines. This page pulls together the background, the mechanisms, and the practical points readers ask about most.
Updated 2025-08-13. Numbers and descriptions here follow the published literature rather than marketing material.
The mechanisms attributed to semax are inferred from animal and cell studies rather than traced to one confirmed target. The most frequently cited pathway involves increased expression of brain-derived neurotrophic factor and nerve growth factor in hippocampal and cortical tissue. Some work points to engagement of melanocortin receptors, particularly MC4, which the parent ACTH fragment can activate. Effects on dopaminergic and serotonergic signalling have also been reported. No single account explains all observed results, and the relative weight of each pathway remains unsettled.
Published studies examine a fairly narrow set of endpoints. Rodent experiments commonly measure maze learning, infarct volume after induced ischemia, and tissue levels of neurotrophic factors. Clinical reports from Russian centres describe attention, memory and recovery scores in patients after stroke or transient ischemic attack. Most of those human studies are small and few have been repeated by independent groups. Outcome measures differ between studies, which limits direct comparison.
Circulation time for the peptide is short because peptidases cleave it readily. The Pro-Gly-Pro tail is thought to slow breakdown compared with the bare ACTH fragment, but the gain appears modest. Absorption after intranasal dosing is limited, and only a fraction of a dose is expected to reach the central nervous system. Laboratory concentrations therefore sit well above levels achieved systemically, a gap that complicates translation from bench findings to clinical claims.
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 |
|---|---|---|
| Appearance | White to off-white powder | Lyophilized solid from research suppliers |
| Solubility | Freely soluble in water | Also dissolves in aqueous buffers; solutions are used fresh |
| Typical storage temperature | -20 °C for lyophilized powder | Short-term transport at 2-8 °C is common |
| Common analytical method | Reverse-phase HPLC | Paired with mass spectrometry for identity confirmation |
| Common synonyms | ACTH(4-10) analogue; MEHFPGP | N-terminal methionine retained in the chain |
Quality documentation for research-grade peptide usually includes a certificate of analysis stating purity, identity, and residual counterion content. Batch-to-batch variation in purity and salt form is a recognized issue, and comparisons across suppliers require attention to the exact counterion, for example acetate versus trifluoroacetate. Sequence verification by tandem mass spectrometry provides stronger evidence than a single mass measurement. For any study reporting biological results, the analytical method and the measured purity should be stated explicitly. Independent verification of supplier claims is considered good practice.
Semax is supplied as a lyophilized powder that appears white to off-white. It dissolves readily in water, phosphate-buffered saline, and other aqueous media, which simplifies preparation of working solutions for laboratory use. The nasal products registered in Russia are dilute aqueous solutions, typically around 0.1 percent peptide by weight. Organic solvents are rarely necessary and can complicate handling. Because the peptide is hygroscopic, weighing should be performed quickly and with minimal exposure to ambient humidity.
Semax 是一种人工合成的七肽，氨基酸序列为 Met-Glu-His-Phe-Pro-Gly-Pro，单字母缩写记作 MEHFPGP。它被归类为促肾上腺皮质激素片段 ACTH(4-10) 的结构类似物，但并不天然存在于生物体内。母体片段 ACTH(4-10) 的序列为 Met-Glu-His-Phe-Arg-Trp-Gly，Semax 替换了中间两个残基，并在羧基端延长了 Pro-Gly-Pro 三肽。这种延长被普遍认为能提升分子对肽酶的耐受性。
该化合物于二十世纪八十年代在俄罗斯被开发，相关工作由俄罗斯科学院分子遗传学研究所的研究团队主导。开发目标并非复制 ACTH 的完整激素活性，而是寻找保留其神经作用方向、同时去除促肾上腺皮质激素释放效应的短肽片段。研究记录显示，这一方向促成了多个相关短肽的合成与筛选，而 Semax 是其中被研究最广泛的一个。当地文献常以 Семакс 这一名称指代它。
研究兴趣主要集中在神经营养因子相关的路径上，包括脑源性神经营养因子与神经生长因子的表达变化。部分实验报告称在特定条件下观察到这些因子的水平上升，但具体信号通路和剂量依赖关系仍未完全厘清。多数公开数据来自细胞模型和动物实验，人体对照研究数量有限。因此，该化合物的作用机制在文献中属于活跃讨论，而非已经确立的定论。
MRI for imaging anatomical structures or blood flow do not require contrast agents since the varying properties of the tissues or blood provide natural contrasts. However, for more specific types of imaging, exogenous contrast agents may be given intravenously, orally, or intra-articularly. Most contrast agents are either paramagnetic (e.g.: gadolinium, manganese, europium), and are used to shorten T1 in the tissue they accumulate in, or super-paramagnetic (SPIONs), and are used to shorten T2 and T2* in healthy tissue reducing its signal intensity (negative contrast agents). The most commonly used intravenous contrast agents are based on chelates of gadolinium, which is highly paramagnetic. In general, these agents have proved safer than the iodinated contrast agents used in X-ray radiography or CT. Anaphylactoid reactions are rare, occurring in approx. 0.03–0.1%. Of particular interest is the lower incidence of nephrotoxicity, compared with iodinated agents, when given at usual doses—this has made contrast-enhanced MRI scanning an option for patients with renal impairment, who would otherwise not be able to undergo contrast-enhanced CT. Gadolinium-based contrast reagents are typically octadentate complexes of gadolinium(III). The complex is very stable (log K > 20) so that, in use, the concentration of the un-complexed Gd3+ ions should be below the toxicity limit.
The government adopted a strategic hamlets policy of the kind used in Malaya and Vietnam to restrict the influence of insurgents over the population of rural areas. Local people were forced to relocate to protected villages (PVs) which were strictly controlled and guarded by the government against rebel atrocities. The protected villages were compared by the guerrillas to concentration camps. Some contemporary accounts claim that this interference in the lives of local residents induced many of them who had previously been neutral to support the guerrillas. The war degenerated into rounds of increasing brutality from all three parties involved (ZANU and ZAPU, and the Rhodesian Army). Mike Subritzky, a former New Zealand Army ceasefire monitor in Rhodesia, in 1980 described the war as "both bloody and brutal and brought out the very worst in the opposing combatants on all three sides." A major problem for the Rhodesian state in fighting the Bush War was always a shortage of manpower. Of the 3,000 white men liable for conscription in 1973, only about 1,000 reported when called-up. In February 1978, the Rhodesian Army stated it needed a minimum of 1,041 men to continue combat operations, and of those called up, only 570 reported for duty while the rest chose to move to South Africa. White emigration increased as the state called up more and more men to fight in the war, creating a vicious circle, which gradually limited the capacity of the Rhodesian state to continue the war.
The oxides and peroxides for these alkali metals do exist, but do not form upon direct reaction of the metal with oxygen at standard conditions. In addition, the small size of the Li+ and O2− ions contributes to their forming a stable ionic lattice structure. Under controlled conditions, however, all the alkali metals, with the exception of francium, are known to form their oxides, peroxides, and superoxides. The alkali metal peroxides and superoxides are powerful oxidising agents. Sodium peroxide and potassium superoxide react with carbon dioxide to form the alkali metal carbonate and oxygen gas, which allows them to be used in submarine air purifiers; the presence of water vapour, naturally present in breath, makes the removal of carbon dioxide by potassium superoxide even more efficient. All the stable alkali metals except lithium can form red ozonides (MO3) through low-temperature reaction of the powdered anhydrous hydroxide with ozone: the ozonides may be then extracted using liquid ammonia. They slowly decompose at standard conditions to the superoxides and oxygen, and hydrolyse immediately to the hydroxides when in contact with water. Potassium, rubidium, and caesium also form sesquioxides M2O3, which may be better considered peroxide disuperoxides, [(M+)4(O2−2)(O−2)2]. Rubidium and caesium can form a great variety of suboxides with the metals in formal oxidation states below +1.
Sources: en.wikipedia.org
=== Legal status === In April 2021, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Adtralza, intended for the treatment of moderate‑to‑severe atopic dermatitis. The applicant for this medicinal product is LEO Pharma A/S. Tralokinumab was approved for medical use in the European Union in June 2021.
The fur is soft, with dense underfur and long, coarse, thick guard hairs. The fur is not as shaggy or coarse as that of brown bears. American black bear skins can be distinguished from those of Asian black bears by the lack of a white blaze on the chest and hairier footpads. Despite their name, black bears show a great deal of color variation. Individual coat colors can range from white, blonde, cinnamon, light brown or dark chocolate brown to jet black, with many intermediate variations existing. Silvery-gray American black bears with a blue luster (found mostly on the flanks) occur along a portion of coastal Alaska and British Columbia. White to cream-colored American black bears occur in the coastal islands and the adjacent mainland of southwestern British Columbia. Albino individuals have also been recorded. Black coats tend to predominate in humid areas, such as Maine, New England, New York, Tennessee, Michigan and western Washington. Approximately 70% of all American black bears are black, though only 50% in the Rocky Mountains are black. Many in northwestern North America are cinnamon, blonde or light brown in color and thus may sometimes be mistaken for grizzly bears. Grizzly (and other types of brown) bears can be distinguished by their shoulder hump, larger size and broader, more concave skull. In his book The Great Bear Almanac, Gary Brown summarized the predominance of black or brown/blonde specimens by location:
Aminoglycoside resistance is generally mediated by a resistance gene that inactivates the antibiotic via chemical modification. A wide range of such aminoglycoside modifying enzymes are known, including nucleotidyltranferases, phosphotransferases, or acetyltransferases: all enzymes that attach extra chemical groups to the molecule. New antibiotics have been developed based on the knowledge of some of these enzymes, incorporating structural changes that prevent specific groups of resistance enzymes from modifying the drug.
Re-lactation is the process of restarting breastfeeding. In developing countries, mothers may restart breastfeeding after a weaning as part of an oral rehydration treatment for diarrhea. In developed countries, re-lactation is common after early medical problems are resolved, or because a mother changes her mind about breastfeeding. Re-lactation is most easily accomplished with a newborn or with a baby that was previously breastfeeding; if the baby was initially bottle-fed, the baby may refuse to suckle. If the mother has recently stopped breastfeeding, chances are higher that the milk supply will return and be adequate. Although some mothers successfully re-lactate after months-long interruptions, success is higher for shorter interruptions. Techniques to promote lactation include frequent attempts to breastfeed, extensive skin-to-skin contact with the baby, and frequent, long pumping sessions. Suckling may be encouraged with a tube filled with infant formula, so that the baby associates suckling at the breast with food. A dropper or syringe without the needle may be used to place milk onto the breast while the baby suckles. The mother should allow the infant to suckle at least ten times during 24 hours, and more times if the baby is interested. These times can include every two hours, whenever the baby seems interested, longer at each breast, and when the baby is sleepy, when they might suckle more readily. In keeping with increasing contact between mother and child, including increasing skin-to-skin contact, grandmothers should pull back and help in other ways.
Sources: en.wikipedia.org
It consists mainly of animal experiments and small clinical reports, with much of the clinical material published in Russian-language journals. Large independent trials are scarce. Separating reliable effects from chance findings is consequently difficult.
A fraction of an intranasal dose is thought to reach the central nervous system, and this route is favoured partly for that reason. The proportion is not well characterized. Direct measurement in humans remains difficult with current methods.
Raised BDNF and NGF expression has been reported across several animal studies, which makes the signal fairly consistent. Whether the same change occurs in humans at usable doses is not established. It is best treated as a working hypothesis rather than a confirmed clinical mechanism.
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.