Envelta (enkephalin intranasal) / Virpax Pharma - LARVOL DELTA

Combining Leu-enkephalin nanomedicines with enkephalinase inhibitors: a promising painkiller strategy? (PubMed, Drug Deliv Transl Res) - "This study investigates the potential of a novel nanomedicine approach relying on squalene nanoparticles of endogenous enkephalinase inhibitors (EEI) - opiorphin (OPN) and STR-324 - to alleviate pain by potentiating the action of enkephalins in vivo, in a model of acute inflammatory pain. EEI-SQ NPs administered subcutaneously successfully enhanced the anti-hyperalgesic effect of LENK-SQ NPs. However, it was considered as not relevant enough regarding the observed local toxicity."

Journal • Pain • PENK

Idiopathic Atraumatic Renal Hemorrhage: Case Report. (PubMed, Clin Pract Cases Emerg Med) - "Wunderlich syndrome is a spontaneous renal or perinephric hemorrhage occurring in the absence of trauma; it is rarely included in the differential for patients with flank pain but can become life-threatening when not recognized."

Journal • Hematological Disorders • Mood Disorders • Pain

Examining the Effect of an Anion-Binding Reagent on the Structure of Deprotonated Leucine Enkephalin Using Cryogenic-Ion Infrared Action Spectroscopy. (PubMed, J Phys Chem A) - "Instead, DIP only partially coordinates with the carboxylate moiety and is positioned below the backbone turn of YGGFL to engage in additional hydrogen bonding interactions. These findings underscore the stability of the turn structure and the strong energetic penalty imposed by disruption of this motif even when strong intermolecular coordination is expected."

Journal

Active Humidity Control Chamber for Desorption Electrospray Ionization-Mass Spectrometry Imaging Applications. (PubMed, J Am Soc Mass Spectrom) - "Preliminary characterization demonstrated differential analyte responses across a range of set points, with observed enhancement of leucine-enkephalin, sulfadimethoxine (negative mode), and maltose (positive mode) in response to increased humidity. The measurable differences in analyte signals across discrete humidity set points underscore the importance of environmental control in ambient ionization strategies. The humidity control system outlined here can be translated to other DESI platforms, with construction information provided herein."

Journal

Idiopathic bilateral renal hemorrhage: Wunderlich Syndrome (UAA 2025) - "It is typically accompanied by acute flank pain, a flank mass, and hypovolemic shock, known as Lenk's triad...In conclusion, it is crucial to recognise perinephric haemorrhage, which can resemble WS, and CECT should be the standard imaging modality for diagnosis."

Cardiovascular • CNS Disorders • Genito-urinary Cancer • Infectious Disease • Nephrology • Renal Cell Carcinoma • Solid Tumor • Vasculitis

Idiopathic bilateral renal hemorrhage: Wunderlich Syndrome: A Case report (UAA 2025) - "It is typically accompanied by acute flank pain, a flank mass, and hypovolemic shock, known as Lenk's triad...In conclusion, it is crucial to recognise perinephric haemorrhage, which can resemble WS, and CECT should be the standard imaging modality for diagnosis."

Case report • Clinical • Cardiovascular • CNS Disorders • Genito-urinary Cancer • Infectious Disease • Nephrology • Renal Cell Carcinoma • Solid Tumor • Vasculitis

Involvement of enkephalinergic system in the reproductive stress response of the gecko Hemidactylus frenatus. (PubMed, Psychoneuroendocrinology) - "Nonetheless, the functional importance of the two forms of enkephalins, methionine-enkephalin (M-ENK) and leucine-enkephalin (L-ENK), remains inadequately understood in the context of the reproductive stress response in reptiles...In the second experiment, the administration of mu or delta opioid receptor antagonists, naltrexone or naltrindole, respectively, reinstated the stress-induced reduction of gonadotropin-releasing hormone immunoreactivity in the hypothalamus, ME, and PD. These treatments also restored the presence of stage IV and V (vitellogenic) follicles, which were absent in the stress-only group. The findings for the first time indicate the activation of enkephalinergic system in the hypothalamus, ME, and PD during the stress response and suggest that the stress-induced suppression of the seasonal ovarian recrudescence phase is attenuated through the administration of mu or delta opioid receptor antagonists in reptiles."

Journal • PENK

A CASE REPORT ON WUNDERLICH SYNDROME IN A 32-YEAR-OLD MALE: DIAGNOSTIC AND CLINICAL CHALLENGES (ERA 2025) - "Classic symptoms of flank mass, flank pain and hypovolemic shock makes up for the Lenk triad seen in less than a quarter of patients... Among the plethora of causes responsible for left flank pain, Wunderlich Syndrome, needs due consideration while ruling out the common differentials. The timing and choice of diagnostic imaging is important, as it helps guide treatment by identifying the cause of the disease. However, if the patient has life- threatening symptoms, imaging may be delayed until the patient's condition has stabilized."

Case report • Clinical • Cardiovascular • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hepatology • Infectious Disease • Kidney Cancer • Nephrology • Oncology • Pain • Renal Calculi • Renal Cell Carcinoma • Solid Tumor

A CASE REPORT ON WUNDERLICH SYNDROME IN A 32-YEAR-OLD MALE: DIAGNOSTIC AND CLINICAL CHALLENGES (ERA 2025) - "Classic symptoms of flank mass, flank pain and hypovolemic shock makes up for the Lenk triad seen in less than a quarter of patients... Among the plethora of causes responsible for left flank pain, Wunderlich Syndrome, needs due consideration while ruling out the common differentials. The timing and choice of diagnostic imaging is important, as it helps guide treatment by identifying the cause of the disease. However, if the patient has life- threatening symptoms, imaging may be delayed until the patient's condition has stabilized."

Case report • Clinical • Cardiovascular • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hepatology • Infectious Disease • Kidney Cancer • Nephrology • Oncology • Pain • Renal Calculi • Renal Cell Carcinoma • Solid Tumor

WUNDERLICH SYNDROME IN ADOLESCENCE: A CASE REPORT (SCCM 2025) - "The classic symptom complex includes flank pain, a flank mass, and hypovolemic shock, known as Lenk's triad, but this is seen in only a small subset of patients...Following the initiation of antibiotic therapy with ceftriaxone and subsequent laboratory and imaging evaluations, suspicion of Wunderlich syndrome was raised due to a grade V renal laceration with perirenal hemorrhage, without a history of trauma... We report a rare case most prevalent in adult pacients. This case report aims to alert pediatricians and clinicians to the possibility of this syndrome occurring in adolescents."

Case report • Clinical • Hematological Disorders • Mood Disorders • Nephrology • Pain • Pediatrics

A spontaneous rupture of a simple renal cyst complicated by hemorrhagic shock: a case report. (PubMed, Ann Med Surg (Lond)) - "Spontaneous retroperitoneal hemorrhages may stem from various pathologies, including simple renal cysts, and frequently manifest with Lenk's triad...Although simple renal cysts are generally asymptomatic, they can lead to serious complications such as hemorrhage that could be life-threatening without appropriate medical intervention. The treatment involves performing an emergency nephrectomy for hemostasis, along with implementing resuscitation measures."

Journal • Hematological Disorders

A Case of Wunderlich Syndrome Caused by Pyelonephritis Due to Klebsiella pneumoniae. (PubMed, Cureus) - "Wunderlich syndrome, characterized by spontaneous nontraumatic renal hemorrhage, is a rare but severe condition often presenting with Lenk's triad: acute abdominal pain, flank mass, and hypovolemic shock...Despite initial antimicrobial therapy, the patient's condition deteriorated, requiring surgical drainage. This case emphasizes the importance of considering surgical intervention in addition to antimicrobial treatment in managing Wunderlich syndrome, especially in patients with pre-existing conditions like diabetes mellitus, which increases the risk of severe complications."

Journal • Diabetes • Hematological Disorders • Infectious Disease • Metabolic Disorders • Nephrology • Oncology • Pain • Pneumonia • Septic Shock

Collision cross sections of large positive fullerene molecular ions and their use as ion mobility calibrants in trapped ion mobility mass spectrometry. (PubMed, Anal Bioanal Chem) - "This study describes the determination of CCS values of fullerene molecular ions from C56+• to C240+• and the application of ions from C56+• to C220+• to calibrate the ion mobility scale of a Bruker timsTOFflex instrument in any combination of LDI, matrix-assisted laser desorption/ionization (MALDI), and electrospray ionization (ESI) modes in the CCS range from about 200 to 420 Å2. This use was exemplified along with ions from Agilent Tune Mix, leucine-enkephalin, angiotensin I, angiotensin II, and substance P."

Journal

Gegen Qinlian decoction alleviates depression-like behavior by modulating the gut microenvironment in CUMS rats. (PubMed, BMC Complement Med Ther) - "Our findings provide evidence supporting the therapeutic efficacy of GQD in alleviating depression-like behavior in CUMS rats, potentially being targeted on colon bacteria (especially the abundance of Ruminococcus and Bacteroides) and metabolites (especially the level of Oleanolic acid)."

Journal • Preclinical • CNS Disorders • Depression • Gastrointestinal Disorder • Mood Disorders • Psychiatry • PENK

A nanomedicine approach for the treatment of long-lasting pain. (PubMed, J Control Release) - "This study explores the potential of a nanomedicine approach, using Leu-enkephalin-squalene nanoparticles (LENK-SQ NPs) for managing long-lasting pain. On the other hand, the biodistribution of fluorescently labelled LENK-SQ NPs revealed their selective accumulation in the incised paw within the first hour post administration, followed by a disassembly of the NPs, starting 24 h later. The study proposes the following multi-step mechanism for the anti-nociceptive pharmacological activity of LENK-SQ NPs: (i) protection of the neuropeptide from metabolization into the bloodstream, (ii) targeted accumulation of the nanoparticles within the incised painful tissue and (iii) gradual release of LENK at the onset of the inflammatory process, leading to the observed analgesic activity."

Journal • Pain

Amadori and Heyns rearrangement products of bioactive peptides as potential new ligands of galectin-3. (PubMed, Carbohydr Res) - "The binding interactions between galectin-3 and the Amadori and Heyns compounds of leucine-enkephalin (YGGFL), leucine-enkephalin methyl ester (YGGFL-OMe), truncated enkephalin (YGG and Y) and tetrapeptide (LSKL) were measured using the AlphaScreen competitive binding assay. The affinity of galectin-3 for Amadori and Heyns compounds depends on both the sugar moiety and the amino acid sequence of the model compounds. The best results were obtained with Leu-enkephalin derivatives of Amadori (IC50 = 6.06 μm) and Heyns (IC50 = 8.6 μm) compound, respectively."

Journal

Photodissociation of leucine-enkephalin protonated peptide: an experimental and theoretical perspective. (PubMed, RSC Adv) - "In general, we observe the same mechanisms as for smaller peptides or protonated Tyr and Phe, that are not quenched by the presence of other amino acids. Nevertheless, we also found some differences, as for H loss, in part due to the fact that the charge is solvated by the peptide chain and not only by the COOH terminal group."

Journal

Organization of enkephalinergic neuronal system in the central nervous system of the gecko Hemidactylus frenatus. (PubMed, Brain Struct Funct) - "This study reports the organization of the methionine-enkephalin (M-ENK) and leucine-enkephalin (L-ENK) neuronal systems in the central nervous system of the gecko Hemidactylus frenatus using an immunofluorescence labeling method. The enkephalinergic fibers were also seen in the area X around the central canal, as well as the dorsal and ventral horns. The widespread distribution of enkephalin-containing neurons within the central nervous system implies that enkephalins regulate a variety of functions in the gecko, including sensory, behavioral, hypophysiotropic, and neuroendocrine functions."

Journal • CNS Disorders • Pain • Solid Tumor

The opioid peptide leucine enkephalin modulates hypothalamic-hypophysial axis in the cichlid fish Oreochromis mossambicus. (PubMed, Anim Reprod Sci) - "This effect appears to be mediated through the suppression of testicular steroidogenesis and the reduction of LH release in the pituitary gland of tilapia. The findings also suggest that elevated L-ENK levels in teleosts may exert their inhibitory influence on the hypophysial-testicular axis via glucocorticoids."

Journal • AR

Wunderlich syndrome in a patient with pyelonephritis. (PubMed, BMJ Case Rep) - "Her atraumatic subcapsular haematoma fulfils two out of three clinical features of Lenk's triad (acute flank pain, hypovolaemic shock), suggestive of Wunderlich syndrome. Urine and blood cultures grew Klebsiella pneumoniae and she was managed conservatively with culture-directed antibiotics, fluids and blood products.Wunderlich syndrome is a rare complication of pyelonephritis and should be considered in patients with pyelonephritis who develop acute severe flank pain, Hb drop and haemodynamic instability. Appropriate medical and surgical therapies need to be instituted early to ensure good outcomes."

Journal • Hematological Disorders • Hypotension • Infectious Disease • Kidney Cancer • Mood Disorders • Nephrology • Oncology • Pain • Pneumonia • Renal Cell Carcinoma • Solid Tumor

Effects of Nano-Electrospray Ionization Emitter Position on Unintentional In-Source Activation of Peptide and Protein Ions. (PubMed, J Am Soc Mass Spectrom) - "A similar effect is observed for CID of the singly protonated leucine enkephalin peptide and Shiga toxin 1 subunit B homopentamer on the Waters Synapt G2-Si instrument. In-source activation effects on a Waters Synapt G2-Si are also investigated by examining the RMSD between CIU fingerprints acquired at different emitter positions and the shifts in CIU50 for structural transitions of bovine serum albumin and NIST monoclonal antibody."

Journal • MB

A Novel Leu-Enkephalin Prodrug Produces Pain-Relieving and Antidepressant Effects. (PubMed, Mol Pharm) - "Leucine-enkephalin (Leu-ENK), the endogenous delta opioid receptor agonist, controls pain and mood and produces potent analgesia with reduced adverse effects compared to conventional opioids. The pain-alleviating effect of KK-103 primarily resulted from activating the delta opioid receptor after the likely conversion of KK-103 to Leu-ENK in vivo. Finally, KK-103 produced an antidepressant-like activity comparable to the antidepressant desipramine, but with minimal gastrointestinal inhibition and no incidence of sedation."

Journal • Addiction (Opioid and Alcohol) • Anesthesia • CNS Disorders • Depression • Gastrointestinal Disorder • Pain • Psychiatry

Research of the analgesic effects and central nervous system impact of electroacupuncture therapy in rats with knee osteoarthritis. (PubMed, Heliyon) - "SD rats were rolled into the blank group, model group (KOA), control group (duloxetine 500 mg/kg/d, Ctrl), conventional EA group, and TDTS-EA group. The Lequesne MG score and midbrain DA, NE, 5-HT, β-EP, and synovial tissue IL-1β expression were decreased in TDTS-EA group versus EA group (P < 0.05). EA can effectively improve the behavioral score of KOA and participate in central analgesia by regulating central DA, NE, 5-HT, β-EP, and L-ENK."

Journal • Preclinical • Immunology • Osteoarthritis • Pain • Rheumatology • IL1B

Transition Metal Ion FRET-Based Probe to Study Cu(II)-Mediated Amyloid-β Ligand Binding. (PubMed, J Am Chem Soc) - "Here, we deploy a combined transition metal ion Förster resonance energy transfer (tmFRET) and native ion mobility-mass spectrometry (IM-MS) approach to characterize the structure of mass- and charge-selected Aβ complexes with Cu(II) ions (a quencher) and a potential aggregation inhibitor, a small neuropeptide named leucine enkephalin (LE)...This allows us to employ tmFRET to probe the binding even in low-abundance and transient Aβ-inhibitor-metal ion complexes. Complementary intramolecular distance and global shape information from tmFRET and native IM-MS, respectively, confirmed Cu(II) displacement toward the N-terminus of Αβ, which discloses the binding region and the inhibitor's orientation."

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Allele-Specific Knockout of a Dominant Gain-of-Function Variant by CRISPR-Cas9 in a Mouse Model of SCN8A-DEE (AES 2023) - "Long-term reduction of Scn8a mRNA using ASO or shRNA protects against seizures in mouse models of DEE (Lenk et al Ann Neurol 2020, and submitted)... Allele-specific CRISPR-Cas9 inactivation of 25% of mutant Scn8a alleles is attainable in brain of heterozygous mutant mice and is sufficient to rescue seizures and survival in a mouse model of SCN8A-DEE."

Preclinical • CNS Disorders • Developmental Disorders • Epilepsy • Genetic Disorders • SCN8A