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Frontiers in Behavioral Neuroscience 2024Drug seeking behavior occurs in response to environmental contexts and drug-associated cues. The presence of these pervasive stimuli impedes abstinence success....
BACKGROUND
Drug seeking behavior occurs in response to environmental contexts and drug-associated cues. The presence of these pervasive stimuli impedes abstinence success. β-adrenergic receptors (β-ARs) have a long-standing historical implication in driving processes associated with contextual memories, including drug-associated memories in substance use disorders. However, sex differences in the role of β-adrenergic receptors in drug memories remain unknown.
HYPOTHESIS
Prior reports indicate a selective role for β2-ARs in retrieval and retention of contextual drug memories in males, and substantial sex differences exist in the expression of β-ARs of male and female rats. Therefore, we hypothesized that there are sex differences in selective recruitment of β-ARs during different stages of memory encoding and retrieval.
METHODS
The role of β-ARs in driving retrieval and learning of contextual cocaine memories was investigated using cocaine conditioned place preference (CPP) in adult male and female Sprague-Dawley rats. Rats were infused directly to the dorsal hippocampus with Propranolol (β1 and β2) or ICI-118,551 (β1) and/or Betaxolol (β2), immediately prior to testing (retrieval), or paired to each cocaine (10 mg/kp, IP) conditioning session (learning).
RESULTS
In males, administration of either β1, β2, or combined β1 and β2-ARs before the initial CPP testing reduced the expression of a CPP compared to vehicle administration. In females, β2-ARs transiently decreased CPP memories, whereas β1 had long lasting but not immediate effects to decrease CPP memories. Additionally, β1 and combined β1 and β2-ARs had immediate and persistent effects to decrease CPP memory expression. DG Fos + neurons predicted cocaine CPP expression in males, whereas CA1 and CA3 Fos + neurons predicted cocaine CPP expression in females.
CONCLUSION
There are significant sex differences in the role of dorsal hippocampus β-ARs in the encoding and expression of cocaine conditioned place preference. Furthermore, sub regions of the dorsal hippocampus appear to activate differently between male and female rats during CPP. Therefore DG, CA3, and CA1 may have separate region- and sex-specific impacts on driving drug- associated, or context-associated cues.
PubMed: 38807929
DOI: 10.3389/fnbeh.2024.1379866 -
BMC Pediatrics May 2024Lip infantile hemangiomas tend to show less volumetric regression and are more susceptible to visible sequelae in the involuted stage. Some of them still require...
BACKGROUND
Lip infantile hemangiomas tend to show less volumetric regression and are more susceptible to visible sequelae in the involuted stage. Some of them still require surgical management after propranolol therapy. This study aimed to evaluate the efficacy and safety of the Stepwise, Multi-Incisional, and Single-Stage (SMISS) approach applied to lip reduction for those with involuted lip hemangiomas.
METHODS
A retrospective review was performed to evaluate patients with lip hemangioma who received previous propranolol treatment and underwent the aforementioned procedure. Demographic characteristics, lesion morphology, and medical history were reviewed. The Visual Analog Scale was applied to assess the postoperative appearance. Complications within 12 months postoperatively were recorded.
RESULTS
A total of 18 patients with lip hemangioma were eligible. All patients received oral propranolol therapy before surgery, with treatment duration ranging from 6.0 to 23.0 months. Their age at surgery ranged from 2.5 to 9.0 years. The median Visual Analog Scale scores were 8.0, ranging from 4.0 to 10.0. No severe complications were reported.
CONCLUSIONS
This modified technique based on the SMISS approach has proven reliable and effective in improving the aesthetic outcome for involuted lip infantile hemangiomas. Practical surgical techniques still play an important part in the propranolol era.
Topics: Humans; Retrospective Studies; Male; Female; Hemangioma; Lip Neoplasms; Propranolol; Child, Preschool; Child; Infant; Lip; Treatment Outcome; Lipoma
PubMed: 38807073
DOI: 10.1186/s12887-024-04838-4 -
Clinical, Cosmetic and Investigational... 2024An infantile hemangioma is a congenital benign tumor formed by the proliferation of vascular cells during the embryonic stage. It is more common in the skin but can also...
An infantile hemangioma is a congenital benign tumor formed by the proliferation of vascular cells during the embryonic stage. It is more common in the skin but can also occur in the mucous membranes, liver, brain and muscle. Hepatic hemangioma appears to be a benign tumor; however, it may lead to poor outcomes because of severe complications, such as high-output cardiac failure. The main treatment of hepatic hemangioma in infants is oral drugs, such as propranolol and glucocorticoids, but the clinical response is not always satisfactory. We describe a rare case of a 2-month-old boy who presented with infantile cutaneous and hepatic hemangiomas. By using dermoscopy and observations of the abdominal color Doppler ultrasound, after 9 months of oral treatment with itraconazole solution, the infantile cutaneous hemangioma complicated with hepatic hemangioma was eventually cured. There was no liver or kidney function damage during the whole treatment period. Itraconazole oral solution for the treatment of infantile cutaneous hemangioma complicated with hepatic hemangioma showed good efficacy, compliance, and safety in this case.
PubMed: 38803817
DOI: 10.2147/CCID.S462665 -
Narra J Apr 2024Budd-Chiari syndrome is one of the post-hepatic causes of portal hypertension and a potential obstruction causes liver fibrosis. In pregnancy, obstruction of hepatic...
Budd-Chiari syndrome is one of the post-hepatic causes of portal hypertension and a potential obstruction causes liver fibrosis. In pregnancy, obstruction of hepatic veins could occur due to stenosis or thrombosis. Variceal bleeding is the most fatal complication in pregnancy with co-existing Budd-Chiari syndrome, with 29.4% incidence of abortion and 33.3% perinatal mortality. The aim of this case report was to present the management of non-cirrhotic variceal bleeding in pregnant women with Budd-Chiari syndrome in the early second trimester. We report a pregnant female at 13-14 weeks gestation presented to the hospital with profuse hematemesis. Doppler ultrasonography (USG) was utilized to confirm the diagnosis of Budd-Chiari syndrome-hepatic vein occlusion type in pregnancy. Abdominal USG revealed hepatomegaly with hepatic veins dilation, while endoscopy showed grade IV esophageal varices and grade IV gastric varices. Laboratory results indicated disseminated intravascular coagulation due to hemorrhage. The patient was given strict fluid resuscitation and three packed red cells transfusion to stabilize the hemodynamic. Bleeding was successfully managed by intravenous octreotide, tranexamic acid, and vitamin K. The case highlights that the management of non-cirrhotic variceal bleeding in pregnancy with Budd-Chiari syndrome requires a multidisciplinary approach and regular fetal monitoring to ensure optimal outcomes.
Topics: Humans; Female; Budd-Chiari Syndrome; Pregnancy; Pregnancy Trimester, Second; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Adult; Pregnancy Complications, Cardiovascular
PubMed: 38798860
DOI: 10.52225/narra.v4i1.245 -
Experimental and Molecular Pathology May 2024pathological pain and Attention-deficit/hyperactivity disorder (ADHD) are two complex multifactorial syndromes. The comorbidity of ADHD and altered pain perception is...
pathological pain and Attention-deficit/hyperactivity disorder (ADHD) are two complex multifactorial syndromes. The comorbidity of ADHD and altered pain perception is well documented in children, adolescents, and adults. According to pathophysiological investigations, the dopaminergic system's dysfunction provides a common basis for ADHD and comorbid pain. Growing evidence suggests that oxidative stress may be crucial in both pathologies. Recent studies revealed that a small peptide encompassing the redox-active site of selenoprotein T (PSELT), protects dopaminergic neurons and fibers as well as lesioned nerves in animal models. The current study aims to examine the effects of PSELT treatment on ADHD-like symptoms and pain sensitivity, as well as the role of catecholaminergic systems in these effects. Our results demonstrated that intranasal administration of PSELT reduced the hyperactivity in the open field, decreased the impulsivity displayed by 6-OHDA-lesioned male mice in the 5-choice serial reaction time task test and improved attentional performance. In addition, PSELT treatment significantly increased the nociception threshold in both normal and inflammatory conditions. Furthermore, anti-hyperalgesic activity was antagonized with sulpiride pre-treatment, but not by phentolamine, or propranolol pre-treatments. The present study suggests that PSELT reduces the severity of ADHD symptoms in mice and possesses potent antinociceptive effects which could be related to the involvement of D2/D3 dopaminergic receptors.
PubMed: 38797131
DOI: 10.1016/j.yexmp.2024.104905 -
Pharmaceutics May 2024Pharmacy compounding, the art and science of preparing customized medications to meet individual patient needs, is on the verge of transformation. Traditional methods of...
Automated Non-Sterile Pharmacy Compounding: A Multi-Site Study in European Hospital and Community Pharmacies with Pediatric Immediate Release Propranolol Hydrochloride Tablets.
Pharmacy compounding, the art and science of preparing customized medications to meet individual patient needs, is on the verge of transformation. Traditional methods of compounding often involve manual and time-consuming processes, presenting challenges in terms of consistency, dosage accuracy, quality control, contamination, and scalability. However, the emergence of cutting-edge technologies has paved a way for a new era for pharmacy compounding, promising to redefine the way medications are prepared and delivered as pharmacy-tailored personalized medicines. In this multi-site study, more than 30 hospitals and community pharmacies from eight countries in Europe utilized a novel automated dosing approach inspired by 3D printing for the compounding of non-sterile propranolol hydrochloride tablets. CuraBlend excipient base, a GMP-manufactured excipient base (pharma-ink) intended for automated compounding applications, was used. A standardized study protocol to test the automated dosing of tablets with variable weights was performed in all participating pharmacies in four different iterative phases. Integrated quality control was performed with an in-process scale and NIR spectroscopy supported by HPLC content uniformity measurements. In total, 6088 propranolol tablets were produced at different locations during this study. It was shown that the dosing accuracy of the process increased from about 90% to 100% from Phase 1 to Phase 4 by making improvements to the formulation and the hardware solutions. The results indicate that through this automated and quality controlled compounding approach, extemporaneous pharmacy manufacturing can take a giant leap forward towards automation and digital manufacture of dosage forms in hospital pharmacies and compounding pharmacies.
PubMed: 38794340
DOI: 10.3390/pharmaceutics16050678 -
Pharmaceutics May 2024Chitosan-triphosphate (TPP) nanogels are widely studied drug delivery carrier systems, typically prepared via a simple mixing process. However, the effects of the...
Chitosan-triphosphate (TPP) nanogels are widely studied drug delivery carrier systems, typically prepared via a simple mixing process. However, the effects of the processing factors on nanogel production have not been extensively explored, despite the importance of understanding and standardising such factors to allow upscaling and commercial usage. This study aims to systematically evaluate the effects of various fabrication and processing factors on the properties of nanogels using a Design of Experiment approach. Hydrodynamic size, polydispersity index (PDI), zeta potential, and encapsulation efficiency were determined as the dependent factors. The temperature, stirring rate, chitosan grade, crosslinker choice, and the interaction term between temperature and chitosan grade were found to have a significant effect on the particle size, whereas the effect of temperature and the addition rate of crosslinker on the PDI was also noteworthy. Moreover, the addition rate of the crosslinker and the volume of the reaction vessel were found to impact the encapsulation efficiency. The zeta potential of the nanogels was found to be governed by the chitosan grade. The optimal fabrication conditions for the development of medium molecular weight chitosan and TPP nanogels included the following: the addition rate for TPP solution was set at 2 mL/min, while the solution was then stirred at a temperature of 50 °C and a stirring speed of 600 rpm. The volume of the glass vial used was 28 mL, while the stirrer size was 20 mm. The second aim of the study was to evaluate the potential for scaling up the nanogels. Size and PDI were found to increase from 128 nm to 151 nm and from 0.232 to 0.267, respectively, when the volume of the reaction mixture was increased from 4 to 20 mL and other processing factors were kept unchanged. These results indicate that caution is required when scaling up as the nanogel properties may be significantly altered with an increasing production scale.
PubMed: 38794324
DOI: 10.3390/pharmaceutics16050662 -
Management of Neonatal Hepatic Hemangiomas: A Single-Center Experience Focused on Challenging Cases.Journal of Clinical Medicine May 2024: Management of hepatic hemangioma (HH) in infancy ranges from close monitoring to surgical resection. We analyzed the clinical characteristics and outcomes of HH...
: Management of hepatic hemangioma (HH) in infancy ranges from close monitoring to surgical resection. We analyzed the clinical characteristics and outcomes of HH according to its treatment options, with particular focus on challenging cases. : Data of patients diagnosed with HHs in their first year of life and followed up for at least 1 year were retrospectively reviewed and divided into treatment and observation groups. Serial imaging results, serum alpha-fetoprotein (AFP) levels, medications, and clinical outcomes were compared. The detailed clinical progress in the treatment group was reviewed separately. : A total of 87 patients (75 in the observation group and 12 in the treatment group) were included. The median HH size at the initial diagnosis and the maximum size were significantly larger in the treatment group than the observation group (2.2 [0.5-10.3] cm vs. 1.0 [0.4-4.0] cm and 2.1 [0.7-13.2] vs. 1.1 [0.4-4.0], respectively; all < 0.05]. The median initial and last serum AFP levels were significantly higher in the treatment group than in the observation group (76,818.7 vs. 627.2 and 98.4 vs. 8.7, respectively; all < 0.05). Serum AFP levels in both groups rapidly declined during the first 3 months of life and were almost undetectable after 6 months. Among the challenging cases, a large (14 × 10 × 6.5 cm sized) focal HH was successfully treated using stepwise medical-to-surgical treatment. : Patients with large HH and mild symptoms can be treated using stepwise pharmacotherapy. More aggressive surgical treatment of tumors unresponsive to initial pharmacotherapy may help shorten the treatment period and improve outcomes.
PubMed: 38792380
DOI: 10.3390/jcm13102839 -
Journal of Cardiovascular Development... May 2024Kawasaki disease (KD) is a type of vasculitis in which giant coronary artery aneurysms (CAAs) can occur. There are no specific guidelines for managing giant CAAs that...
BACKGROUND
Kawasaki disease (KD) is a type of vasculitis in which giant coronary artery aneurysms (CAAs) can occur. There are no specific guidelines for managing giant CAAs that develop quickly and are at risk of rupture. Regarding cardiovascular drugs, only beta-blockers are formally recommended in the acute phase of KD.
CASE PRESENTATION
A 6-month-old male patient with multiresistant Kawasaki disease and giant CAAs that continued to enlarge after controlling systemic inflammation was examined. The patient required three doses of intravenous immunoglobulin, methylprednisolone pulses, and anakinra and infliximab to normalize systemic inflammation. Due to the rapid increment of aneurysms' dimensions and the risk of rupture, we introduced anticoagulant therapy and propranolol plus captopril, and titration doses were introduced according to a tolerated decrease in heart rate and arterial pressure. CAAs increment stabilized and slowly reduced their dimensions.
CONCLUSIONS
The authors describe an atypical case of multiresistant KD with giant rapidly increasing CAAs even after controlling systemic inflammation. The introduction of a beta-blocker and an angiotensin-converting enzyme (ACE) inhibitor was demonstrated to be useful for stabilizing giant CAAs growth and reducing the potential risk of rupture.
PubMed: 38786971
DOI: 10.3390/jcdd11050149 -
Bioactive Materials Sep 2024Tumor-promoting niche after incomplete surgery resection (SR) can lead to more aggressive local progression and distant metastasis with augmented...
Wrecking neutrophil extracellular traps and antagonizing cancer-associated neurotransmitters by interpenetrating network hydrogels prevent postsurgical cancer relapse and metastases.
Tumor-promoting niche after incomplete surgery resection (SR) can lead to more aggressive local progression and distant metastasis with augmented angiogenesis-immunosuppressive tumor microenvironment (TME). Herein, elevated neutrophil extracellular traps (NETs) and cancer-associated neurotransmitters (CANTs, e.g., catecholamines) are firstly identified as two of the dominant inducements. Further, an injectable fibrin-alginate hydrogel with high tissue adhesion has been constructed to specifically co-deliver NETs inhibitor (DNase I)-encapsulated PLGA nanoparticles and an unselective β-adrenergic receptor blocker (propranolol). The two components (i.e., fibrin and alginate) can respond to two triggers (thrombin and Ca, respectively) in postoperative bleeding to gelate, shaping into an interpenetrating network (IPN) featuring high strength. The continuous release of DNase I and PR can wreck NETs and antagonize catecholamines to decrease microvessel density, blockade myeloid-derived suppressor cells, secrete various proinflammatory cytokines, potentiate natural killer cell function and hamper cytotoxic T cell exhaustion. The reprogrammed TME significantly suppress locally residual and distant tumors, induce strong immune memory effects and thus inhibit lung metastasis. Thus, targetedly degrading NETs and blocking CANTs enabled by this in-situ IPN-based hydrogel drug depot provides a simple and efficient approach against SR-induced cancer recurrence and metastasis.
PubMed: 38783926
DOI: 10.1016/j.bioactmat.2024.05.022