Envelta (enkephalin intranasal) / Virpax Pharma - LARVOL DELTA

Tiny Droplets, Large Insights: Studying Peptide Aggregation with Droplet-Based Microfluidics Hyphenated with Ion Mobility Mass Spectrometry. (PubMed, Anal Chem) - "Using model peptides, bradykinin, leucine-enkephalin, and the aggregation-prone segment Ac-PHF6-NH2 from the tau protein, we demonstrated the successful development of a sensitive method. Additionally, using the Ac-PHF6-NH2 peptide, oligomeric transient species were probed and characterized by their IM and m/z values. This work demonstrates the potential of DBMF-IM-MS to study peptide aggregation in confined environments, providing insights into the formation of oligomeric species and laying the groundwork for studies on larger proteins and the development of therapeutic agents targeting aggregation using multichannel devices."

Journal • CNS Disorders • PHF6

An alternative cause of a Leigh-like phenotype: VAC14-related disease (SSIEM 2026) - "Conclusion VAC14-related neurodegenerative disease was first described in 2016 by Lenk et al...Reported cases in the literature remain very limited. This case further expands the clinical spectrum of VAC14-related neurodegenerative disorders."

CNS Disorders • Metabolic Disorders • Movement Disorders

Simulation of peptide retention on dual reversed phase: strong cation exchange functionalized stationary phase gradients. (PubMed, J Chromatogr A) - "Experimental retention data for four representative peptides (valine-tyrosine-valine, methionine enkephalin, leucine enkephalin, and angiotensin II) were collected using uniform C4 and strong cation exchange columns to establish accurate fit parameters for the linear solvent strength and ionic exchange models, respectively. For the conditions tested, the resulting analysis confirmed that a resolution of 2.5 for all critical pairs could be achieved within 15 min across various gradient combinations. The resulting simulations indicate a strong potential for utilizing small, strategic segments of functionalization on stationary phase gradients to significantly enhance separations using traditional mobile phase gradients."

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pH-induced transition of sponge-phase nanoparticles to micelles: The case of Leu-enkephalin-squalene lipopeptide prodrug. (PubMed, J Colloid Interface Sci) - "Self-assembled bioconjugates into nanoparticles (NPs) represent a powerful strategy to enhance drug efficacy. These findings demonstrate that LENK-SQ behaves as a peptide amphiphile (PA) with high versatility in self-assembled morphologies depending on environmental conditions. Beyond addressing how sponge-phase NPs may evolve structurally after intravenous administration, this study opens avenues for investigating the potential influence of self-assembled morphologies on pharmaceutical activity."

Journal • Pain

Fatal Wunderlich Syndrome During Hemodialysis: A Rare Case and Review of the Literature. (PubMed, Cureus) - "Wunderlich syndrome (WS) is a rare but life-threatening condition characterized by spontaneous, non-traumatic renal hemorrhage, which may present with Lenk's triad...Despite initial resuscitative measures, the patient rapidly deteriorated into refractory hemorrhagic shock and died before definitive intervention could be performed. This case highlights the potential for rapid deterioration in hemodialysis patients and underscores the importance of early recognition, rapid imaging, and timely multidisciplinary management."

Journal • ANCA Vasculitis • Chronic Kidney Disease • Hematological Disorders • Nephrology • Pain • Renal Disease • Vasculitis

Immunohistochemical Staining of the Brain of the Tuatara Sphenodon punctatus. (PubMed, Brain Behav Evol) - "These markers include leucine-enkephalin, the preproenkephalin-derived neuropeptide methionine-enkephalin-arg-phe, the preproenkephalin-derived neuropeptide peptide E, substance P, tyrosine hydroxylase, LANT6, neuropeptide Y, glutamic acid decarboxylase, serotonin, vasoactive intestinal polypeptide, luteinizing hormone releasing hormone, and cholecystokinin-8. To show its value, we provide here an overview of the labeling obtained with each antibody, highlighting forebrain and midbrain, which shows remarkable resemblance to that reported in turtles. Images of the labeling will be made available at Brainmaps.org, and the slides will be banked at the Museum of Comparative Zoology at Harvard University, where they can be analyzed in greater depth by interested investigators."

Journal • PENK

Cryogenic Gas-phase IR Spectroscopy on a Commercial Ion Mobility-Mass Spectrometry Platform. (PubMed, Anal Chem) - "The capabilities of this instrument are demonstrated by measuring IM-MS-IR data for leucine enkephalin, a benchmark standard in mass spectrometry...These data demonstrate the first implementation of messenger-tagging IR spectroscopy in a widely used, commercially available IM-MS system. The user-friendly implementation of these techniques overcomes a significant barrier to the widespread incorporation of orthogonal IR spectroscopy measurements in existing IM-MS workflows and will aid in distinguishing unknown molecules in untargeted -omics measurements."

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Wünderlich Syndrome Without Classic Signs: A Case of Spontaneous Retroperitoneal Hemorrhage From a Ruptured Renal Angiomyolipoma. (PubMed, Cureus) - "It has been previously associated with Lenk's triad of flank pain, hematuria, and hypovolemic shock; however, this triad is not always present, making early recognition in the emergency department challenging...This case reinforces that early cross-sectional imaging is essential for diagnosing spontaneous retroperitoneal hemorrhage, enabling timely escalation to interventional management. Prompt recognition, rapid imaging, and expedited access to definitive intervention remain critical determinants of outcome."

Journal • Cardiovascular • Hematological Disorders • Hypotension • Oncology • Pain

A CASE REPORT ON WUNDERLICH SYNDROME IN A 32-YEAR-OLD MALE: DIAGNOSTIC AND CLINICAL CHALLENGES (ISN-WCN 2026) - "Perirenal abscess formation was considered at this time and Ceftriaxone was shifted to Meropenem pending blood culture results...On hospital day 6, repeat CT scan of the whole abdomen with contrast was ordered but due to financial limitations, the patient opted to go home and continue with oral antibiotic Cefixime to complete 2 weeks.One week after discharge, CBC was done showing no further decline of hemoglobin and a follow up abdominal ultrasound showed right perinephric hematoma measuring 11.3 cm x 9.5 cm x 4.1 cm with an estimated volume of 231.51 mL with complete resolution of the pateint's fever...The characteristic Lenk triad of flank mass, a flank pain, and hypovolemic shock is appreciated in only an estimated 20% of patients with WS...Conservative management with follow-up imaging is a good approach to avoid unnecessary surgery. By delving into this rare occurence and its characteristics and clinical outcomes, the goal is to shed insights on the complexities..."

Case report • Clinical • Anorexia • Cardiovascular • Gastroenterology • Gastrointestinal Disorder • Genito-urinary Cancer • Infectious Disease • Kidney Cancer • Nephrology • Renal Calculi • Renal Cell Carcinoma • Renal Disease • Solid Tumor • Vasculitis

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."

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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."

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