Everything below concerns somatotroph. We keep the language plain, cite what the science says, and separate well-supported claims from open questions.
Last reviewed on 2026-03-06. Where a claim depends on a specific study, the study is described rather than over-claimed.
Whether the drug improves hard clinical outcomes is not settled. No completed trial has shown a reduction in heart attacks or strokes among treated patients, although a dedicated cardiovascular outcomes study has been discussed in the literature. Investigators have also examined hepatic fat in people with HIV and fatty liver disease, cognitive measures in small cohorts, and changes in bone density. Regulatory labeling emphasizes monitoring of insulin-like growth factor 1 because supraphysiologic levels raise questions about tissue growth, and the clinical significance of that signal remains an open question rather than a demonstrated harm.
Binding of tesamorelin to the growth hormone-releasing hormone receptor on anterior pituitary somatotrophs activates a Gs protein pathway, raises cyclic AMP, and triggers release of stored growth hormone into the bloodstream. Because the analogue resists dipeptidyl peptidase-4, its plasma residence time exceeds that of native GHRH, producing a larger and more sustained secretory signal. The released growth hormone then acts on the liver and peripheral tissues to raise insulin-like growth factor 1, which feeds back on the hypothalamus and pituitary. This axis explains both the intended effects on fat distribution and the biological markers used to track them.
A Phase 3 program led to regulatory approval in the United States in 2010 for reduction of excess visceral abdominal fat in adults with HIV and lipodystrophy. Subsequent studies examined effects on liver fat, muscle area, and metabolic markers, with mixed findings for some endpoints. Long-term cardiovascular outcomes and effects on mortality remain uncertain because most trials were relatively short and focused on imaging-based fat measurements. Use in populations without HIV has been studied experimentally but is not part of the approved indication.
Tesamorelin is a synthetic analog of growth hormone-releasing hormone, a peptide hormone produced by the hypothalamus. The molecule retains the 44-amino-acid sequence of human GHRH and carries a trans-3-hexenoyl modification at its N-terminus. This modification increases resistance to enzymatic degradation and extends the peptide's functional stability relative to native GHRH. The compound is supplied as a lyophilized powder for reconstitution and subcutaneous administration in clinical settings. Its development code was TH9507, and it belongs to the GHRH analog class. It is not a growth hormone product; instead, it acts upstream to stimulate endogenous growth hormone release.
Clinical interest in tesamorelin arose from the need to address visceral adiposity in people living with HIV. Antiretroviral therapy improved survival but was associated in some patients with central fat accumulation, altered lipid profiles, and metabolic complications. This condition, often called HIV-associated lipodystrophy, involves excess visceral adipose tissue that is difficult to manage through diet and exercise alone. Investigators evaluated tesamorelin because GHRH analogs can stimulate growth hormone secretion and influence fat distribution without direct liposuction or invasive procedures.
| Property | Value | Notes |
|---|---|---|
| Appearance | White to off-white powder | Lyophilized cake in single-use vials |
| Solubility class | Freely soluble in water | Reconstituted with sterile diluent before injection |
| Typical storage temperature | 2 to 8 degrees Celsius | Before reconstitution; protect from light |
| Typical analytical method | Reversed-phase high-performance liquid chromatography | Purity and related-substance testing |
| Identity confirmation | Mass spectrometry | Observed mass near 5.1 kDa for the intact peptide |
Pharmacodynamic studies show that tesamorelin reduces visceral adipose tissue more than subcutaneous adipose tissue in the studied population. This selectivity may relate to differences in blood flow and hormone sensitivity between fat depots. Effects on glucose metabolism and insulin sensitivity have been investigated, with some trials reporting modest changes and others showing stability. The precise relationship between growth hormone exposure, IGF-1 levels, and visceral fat loss remains an active area of analysis.
Tesamorelin binds to growth hormone-releasing hormone receptors on somatotroph cells in the anterior pituitary. Receptor activation increases intracellular cyclic AMP and promotes synthesis and secretion of growth hormone. Because the peptide mimics endogenous GHRH, it amplifies the normal pulsatile release of growth hormone rather than providing exogenous growth hormone directly. This upstream action distinguishes tesamorelin from recombinant growth hormone preparations and from growth hormone secretagogues that act at different receptors.
Stimulated growth hormone release leads to hepatic production of insulin-like growth factor 1, a key mediator of many growth hormone effects. In clinical studies, tesamorelin increased IGF-1 levels in a dose-dependent manner, although the response varies among individuals. The drug's effect on visceral fat is thought to involve growth hormone-mediated lipolysis and altered adipocyte metabolism. Muscle mass and lean body mass have also been assessed as secondary outcomes, but changes are generally smaller and less consistent than fat reductions.
监管记录显示，特沙莫瑞林于 2010 年在美国首次获得批准，用于人类免疫缺陷病毒感染相关的脂肪营养不良患者。批准依据来自降低内脏脂肪的临床试验，而非体重或瘦体重的普遍改善。后续出现了不同制剂版本，但其核心适应症保持一致。关于长期心血管结局和死亡率影响，现有证据仍不充分。
在临床研究之外，特沙莫瑞林常被讨论为生长激素分泌促进剂，但这一说法需要限定。它并不等同于生长激素本身，也不属于普通减重药物。部分研究关注其减少腹部脂肪和改善脂质谱的潜力，另一些研究则关注胰岛素抵抗和 IGF-1 升高等信号。这些效应的临床意义仍在评估中，尚未形成统一结论。
特沙莫瑞林是一种合成肽，其序列与人生长激素释放激素的 44 个氨基酸形式相关。它在 N 端带有反式-3-己烯酰基修饰，这一改动可减缓二肽基肽酶 IV 的降解。该化合物属于生长激素释放激素受体激动剂，可刺激垂体释放生长激素。研究文献通常将其归入合成肽类药物，而非小分子化合物。
质量控制项目一般包括外观、身份、纯度、含量、有关物质、水分和微生物限度。身份确认可通过肽图谱、氨基酸分析和质谱完成，纯度则用面积归一化法计算。研究级材料与药品级材料的要求不同，前者常缺少完整药典验证。不同批次间杂质谱是否影响活性，仍是一个需要具体数据回答的问题。
特沙莫瑞林的检测通常依赖反相高效液相色谱和质谱联用。反相色谱可分离肽主峰与缺失序列、氧化产物等杂质，质谱则提供精确质量以确认身份。对于复杂基质中的定量，常采用液相色谱-串联质谱，并配合固相萃取或蛋白沉淀。生物样品中的肽易降解，因此采集和处理条件会影响结果。
=== Deep learning reconstruction === Deep learning approaches extend traditional acceleration methods by training neural networks on large datasets of paired undersampled and fully-sampled MRI scans, enabling image reconstruction at higher acceleration factors than classical parallel imaging alone. Rather than relying on hand-crafted sparsity priors as in compressed sensing, these models learn reconstruction directly from data. One prominent approach, the end-to-end variational network (E2E-VarNet), combines sensitivity map estimation and iterative refinement in a fully learned pipeline, achieving state-of-the-art reconstruction quality on the fastMRI benchmark for both knee and brain MRI.. The fastMRI initiative, a collaboration between Meta AI Research (FAIR) and NYU Langone Health, established the field's primary open benchmark by releasing over 1.5 million raw MRI measurements from knee, brain, and prostate scans in 2018. Annual fastMRI challenges have benchmarked reconstruction quality across international research teams. A clinical interchangeability study confirmed that deep learning reconstruction at 4× acceleration produces images diagnostically equivalent to fully-sampled acquisitions for knee imaging at 3T, and these methods have since been adopted clinically at major medical centers.
==== Intensification of the Bush War ==== The work of journalists such as Lord Richard Cecil, son of Robert Gascoyne-Cecil, 6th Marquess of Salisbury, stiffened the morale of Rhodesians and their overseas supporters. Lord Richard produced news reports for ITN which typically contrasted the "incompetent" insurgents with the "superbly professional" government troops. A group of ZANLA fighters killed Lord Richard on 20 April 1978 when he was accompanying a Rhodesian airborne unit employed in Fire Force Operations. The shooting down on 3 September 1978 of the civilian Air Rhodesia airliner, a Vickers Viscount named the Hunyani, in the Kariba area by ZIPRA fighters using a surface-to-air missile, with the subsequent massacre of 10 of its 18 survivors, is widely considered to be the event that finally destroyed the Rhodesians' will to continue the war. Although militarily insignificant, the loss of this aircraft (and a second Viscount, named the Umniati, in 1979) demonstrated the reach of resistance movements extended to Rhodesian civil society. The Rhodesians' means to continue the war were also eroding fast. In December 1978, a ZANLA unit penetrated the outskirts of Salisbury and fired a volley of rockets and incendiary device rounds into the main oil storage depot – the most heavily defended economic asset in the country. The storage tanks burned for five days, giving off a column of smoke that could be seen 130 kilometres (80 mi) away. Five hundred thousand barrels (79,000 m3) of petroleum product (comprising Rhodesia's strategic oil reserve) were lost.
Adiponectin enhances insulin sensitivity primarily though regulation of fatty acid oxidation and suppression of hepatic glucose production. Adiponectin is secreted into the bloodstream, where it accounts for about 0.01% of all plasma protein at around 5-10 μg/mL. In adults, plasma concentrations are higher in females than males, and are reduced in diabetics compared to nondiabetics. Weight reduction significantly increases circulating concentrations. Adiponectin automatically self-associates into larger structures. Initially, three adiponectin molecules bind together to form a homotrimer. The trimers continue to self-associate and form hexamers or dodecamers. Like the plasma concentration, the relative levels of the higher-order structures are sexually dimorphic, where females have increased proportions of the high-molecular-weight forms. Recent studies showed that the high-molecular-weight form may be the most biologically active form regarding glucose homeostasis. High-molecular-weight adiponectin was further found to be associated with a lower risk of diabetes with similar magnitude of association as total adiponectin. However, coronary artery disease has been found to be positively associated with high molecular weight adiponectin, but not with low molecular weight adiponectin. Adiponectin exerts some of its weight-reduction effects via the brain. This is similar to the action of leptin; adiponectin and leptin can act synergistically. Adiponectin promoted synaptic and memory function in the brain. Humans with lower levels of adiponectin have reduced cognitive function.
==== Combination formulations ==== Adapalene/benzoyl peroxide (CD-0271/CD-1579; Epiduo; GK-530G; Tactuo; TactuPump) – combination of adapalene (retinoid) and benzoyl peroxide (undefined mechanism of action) Adapalene/benzoyl peroxide/clindamycin phosphate (Cabtreo; IDP-126) – combination of adapalene (retinoid), benzoyl peroxide (undefined mechanism of action), and clindamycin phosphate (lincosamide antibiotic) Benzoyl peroxide/clindamycin (Duac) – combination of benzoyl peroxide (undefined mechanism of action) and clindamycin (lincosamide antibiotic) Benzoyl peroxide/clindamycin low dose (Acanya; BenzaClin; Clin-BPO; Onexton) – combination of benzoyl peroxide (undefined mechanism of action) and clindamycin (lincosamide antibiotic) Benzoyl peroxide/tretinoin – combination of benzoyl peroxide (undefined mechanism of action) and tretinoin (retinoid) Clindamycin/tretinoin (Acnatac; Acnex; CLin-RA; Ziana) – combination of clindamycin (lincosamide antibiotic) and tretinoin (retinoid) Ethinylestradiol/drospirenone low-dose (Yasmin, Yaz) – combination of ethinylestradiol (estrogen) and drospirenone (progestogen) and a combined oral contraceptive Ethinylestradiol/drospirenone/levomefolic acid (BAY98-7071; Beyaz; Safyral; Yasmin Plus; Yaz Flex Plus; Yaz Plus) – combination of ethinylestradiol (estrogen), drospirenone (progestogen), and levomefolic acid (vitamin B9) and a combined oral contraceptive
CD38 (cluster of differentiation 38), also known as cyclic ADP ribose hydrolase, is a glycoprotein found on the surface of many immune cells (white blood cells), including CD4+, CD8+, B lymphocytes and natural killer cells. CD38 also functions in cell adhesion, signal transduction and calcium signaling. In humans, the CD38 protein is encoded by the CD38 gene which is located on chromosome 4. CD38 is a paralog of CD157, which is also located on chromosome 4 (4p15) in humans.
Sources: en.wikipedia.org
The Laténium is an archeology museum located in Laténa, Switzerland. Its name refers to the famous nearby site of La Tène which gave its name to the Second European Iron age. The Laténium is composed of a 2,500 m2 (27,000 ft2) park and a museum building which also harbours the archaeological section of the Heritage Offices of the State of Neuchâtel, as well as the chair of prehistory of the University of Neuchâtel. The museum and its park are built on what used to be three archaeological sites that were excavated during the construction of the A5 motorway. Theses sites date from the Upper Paleolithic, Bronze Age and Neolithic. The park features dolmens and glacial erratics, reconstitutions of prehistoric and antique devices (a La Tène house, a Gallo-Roman ship and a Celtic bridge, notably), and modern works of art. The museum displays the Bevaix boat, a 20 m (66 ft) Gallo-Roman ship found in Bevaix. Items from periods comprised between the Paleolithic to the Middle Ages are on display, including the remains of a Magdalenian hunting camp.
Chief Operating Officer Scott Boatwright was appointed by the board as interim CEO effective August 31, 2024. At the same board meeting, company director Scott Maw was named chairman of the board and retiring CFO Jack Hartung was named president. Four months later, Boatwright was named permanent CEO by the board in November 2024. Chipotle's key management as of January 2026 consists of:
=== Creation of Animal Models === Intracerebroventricular injection has been used to inject drugs that induce a diseased state to create animal models for a variety of diseases. Of these, Alzheimer's disease (AD) animal models are heavily represented in the literature. ICV injection of Streptozotocin has been used to create a metabolic model of Alzheimer's disease. This protocol works by damaging the control level of cerebral glucose metabolism to mimic Alzheimer's disease symptoms. An early sign of AD is glucose hypometabolism and impaired insulin signaling has been seen in AD patients. Streptozotocin has also largely been used to create diabetes animal models, by injecting either intravenously or intraperitoneally. These ICV injections result in models for the sporadic Alzheimer's disease (sAD) form, rather than familial. A characteristic of sAD is an insulin-resistant brain state (IRBS). Streptozotocin is a beta-cytotoxic drug and by injecting it directly into the cerebral ventricles, the treated mice develop symptoms that align with sAD symptoms in humans. Some of these symptoms include IRBS-associated memory impairment, glucose hypometabolism, oxidative stress, and neurodegeneration. More recently, a model for AD that represents both familial and sporadic AD has emerged. In the clinic, as well as independent experiments, an increase in amyloid beta (Aβ) levels in the brain has been seen to cause Alzheimer-like symptoms. To create an animal model of AD, Aβ can be injected using ICV injection.
Androgen receptors Calcitriol receptors Corticotropin-releasing hormone receptor 1 Corticotropin releasing hormone receptor 2 Estrogen receptors Follicle-stimulating hormone receptors Glucagon receptors Gonadotropin receptors Gonadotropin-releasing hormone receptors Growth hormone receptors Insulin receptor Luteinizing hormone Progesterone receptors Retinoid receptors Somatostatin receptors Thyroid hormone receptors Thyrotropin receptors
So, the term "Satsuma ware" came to be associated not with a place of origin but with lower-quality ware created purely for export. Despite this, artists such as Yabu Meizan and Makuzu Kōzan maintained the highest artistic standards while also successfully exporting. From 1876 to 1913, Kōzan won prizes at 51 exhibitions, including the World's fair and the National Industrial Exhibition.
Sources: en.wikipedia.org
Three major genes are involved in determination of Drosophila sex. These are sex-lethal, sisterless, and deadpan. Deadpan is an autosomal gene which inhibits sex-lethal, while sisterless is carried on the X chromosome and inhibits the action of deadpan. An AAX cell has twice as much deadpan as sisterless, so sex-lethal will be inhibited, creating a male. However, an AAXX cell will produce enough sisterless to inhibit the action of deadpan, allowing the sex-lethal gene to be transcribed to create a female. Later, control by deadpan and sisterless disappears and what becomes important is the form of the sex-lethal gene. A secondary promoter causes transcription in both males and females. Analysis of the cDNA has shown that different forms are expressed in males and females. Sex-lethal has been shown to affect the splicing of its own mRNA. In males, the third exon is included which encodes a stop codon, causing a truncated form to be produced. In the female version, the presence of sex-lethal causes this exon to be missed out; the other seven amino acids are produced as a full peptide chain, again giving a difference between males and females. Presence or absence of functional sex-lethal proteins now go on to affect the transcription of another protein known as doublesex. In the absence of sex-lethal, doublesex will have the fourth exon removed and be translated up to and including exon 6 (DSX-M[ale]), while in its presence the fourth exon which encodes a stop codon will produce a truncated version of the protein (DSX-F[emale]).
There are two distinct lysine biosynthetic pathways: the diaminopimelic acid pathway and the α-aminoadipate pathway. The most common of the two synthetic pathways is the diaminopimelic acid pathway; it consists of several enzymatic reactions that add carbon groups to aspartate to yield lysine:
== External links == Kristin Tillotson, "Minnesota Opera co-commissions Cold Mountain, Minneapolis Star Tribune (Artcetera blog), 6 May 2014 Heidi Waleson, "Creating Cold Mountain: Student Singers Help to Shape a Major Modern Opera", Overtones (Curtis Institute of Music), Spring 2014 Cold Mountain, Opera Philadelphia page "Cold Mountain makes East Coast Premiere February 5–14, 2016, at the Academy of Music." Opera Philadelphia press release, 5 January 2016 Tom Huizenga, "Great Expectations: A New Season Of New Music". National Public Radio (Deceptive Cadence blog), 3 September 2014 "Jennifer Higdon writes an opera", The Musicalist podcast, 12 February 2014 Jim Cotter, "Jennifer Higdon on Cold Mountain". WRTI, 90.1 FM, 16 November 2012 Mark Gresham, "Jennifer Higdon completes her new opera, Cold Mountain". EarRelevant blog, 17 September 2013 Pentatone Records page on Cold Mountain Peter Dobrin, "Cold Mountain scores", The Philadelphia Inquirer, Blogs the Arts, 16 May 2016
The Supreme Soviet (successor of the Congress of Soviets) was nominally the highest organ of state authority for most of the Soviet history, at first acting as a rubber stamp institution, approving and implementing all decisions made by the party. However, its powers and functions were extended in the late 1950s, 1960s, and 1970s, including the creation of new state commissions and committees. It gained additional powers relating to the approval of the Five-Year Plans and the government budget. The Supreme Soviet elected a Presidium (successor of the Central Executive Committee) to wield its power between plenary sessions, ordinarily held twice a year, and appointed the Supreme Court, the Procurator General and the Council of Ministers (known before 1946 as the Council of People's Commissars), headed by the Chairman (Premier) and managing an enormous bureaucracy responsible for the administration of the economy and society. State and party structures of the constituent republics largely emulated the structure of the central institutions, although the Russian SFSR, unlike the other constituent republics, for most of its history had no republican branch of the CPSU, being ruled directly by the union-wide party until 1990. Local authorities were organized likewise into party committees, local Soviets and executive committees. While the state was a de jure federation with a nominally federal constitution, the party was de facto centralized and unitary. The state security police (the KGB and its predecessor agencies) played an important role in Soviet politics.
Sources: en.wikipedia.org
It mimics a natural hypothalamic signal that tells the pituitary to release growth hormone. The result is a rise in circulating growth hormone and, indirectly, in insulin-like growth factor 1. Over weeks of treatment this shift is associated with a selective decrease in fat stored inside the abdomen.
The primary measure is usually a cross-sectional abdominal scan that separates internal fat from fat just under the skin. Waist circumference and body weight are recorded as secondary measures because they are easy to obtain but do not distinguish the two fat compartments. Hormone and metabolic blood tests are collected alongside the imaging.
Available follow-up data indicate that visceral fat drifts back toward pretreatment levels once injections stop. The change is therefore best described as treatment-dependent rather than permanent. Investigators continue to debate whether intermittent or repeated courses would preserve any benefit.
It is a synthetic peptide analog of human growth hormone-releasing hormone. It is used clinically to reduce excess visceral abdominal fat in adults with HIV-associated lipodystrophy. It works by stimulating pituitary growth hormone release.