High-dose Injection Research Articles

Revolutionizing rheumatic heart disease prevention: the potential of high-dose subcutaneous benzathine penicillin G: a narrative review

Rheumatic heart disease (RHD) is a severe, chronic condition arising from acute rheumatic fever (ARF), a complication of untreated group A - Streptococcus infections. RHD results in progressive damage to the heart valves, leading to significant morbidity and mortality. While RHD has declined in high-income countries due to effective prophylaxis, it remains a major health issue in developing regions. Approximately 15 million people worldwide are affected by RHD, impacting quality of life and healthcare systems. This narrative review evaluates the efficacy and safety of high-dose subcutaneous benzathine penicillin G (BPG) injections as a preventive strategy for RHD. Traditionally administered intramuscularly, the review explores the subcutaneous route’s benefits. Subcutaneous BPG is effective in preventing ARF recurrences and managing RHD progression. It maintains therapeutic penicillin levels over extended periods, potentially reducing injection frequency. This method is associated with less pain and improved patient adherence compared to intramuscular injections. However, subcutaneous BPG administration has challenges. Adverse effects, such as allergic reactions and anaphylaxis, though infrequent, require careful management. Consistent drug supply is also essential. Future research should explore innovative delivery methods, such as implantable devices or transdermal systems, to further improve patient outcomes. In conclusion, high-dose subcutaneous BPG injections offer a promising option for RHD prophylaxis, combining efficacy with a favorable safety profile. Addressing administration and side effect challenges is crucial for optimizing treatment effectiveness.

Safety of Human USH1C Transgene Expression Following Subretinal Injection in Wild-Type Pigs.

This study aimed to evaluate early-phase safety of subretinal application of AAVanc80.CAG.USH1Ca1 (OT_USH_101) in wild-type (WT) pigs, examining the effects of a vehicle control, low dose, and high dose. Twelve WT pigs (24 eyes) were divided into three groups: four pigs each received bilateral subretinal injections of either vehicle, low dose (3.3 × 1010 vector genomes [vg] per eye), or high dose (1.0 × 1011 vg per eye). Total retinal thickness (TRT) was evaluated using optical coherence tomography and retinal function was assessed with full-field electroretinography (ff-ERG) at baseline and two months post-surgery. After necropsy, retinal changes were examined through histopathology, and human USH1C_a1/harmonin expression was assessed by quantitative PCR (qPCR) and Western blotting. OT_USH_101 led to high USH1C_a1 expression in WT pig retinas without significant TRT changes two months after subretinal injection. The qPCR revealed expression of the human USH1C_a1 transgene delivered by the adeno-associated virus vector. TRT changes were minimal across groups: vehicle (256 ± 21 to 243 ± 18 µm; P = 0.108), low dose (251 ± 32 to 258 ± 30 µm; P = 0.076), and high dose (242 ± 24 to 259 ± 28 µm; P = 0.590). The ff-ERG showed no significant changes in rod or cone responses. Histopathology indicated no severe retinal adverse effects in the vehicle and low dose groups. Early-phase clinical imaging, electrophysiology, and histopathological assessments indicated that subretinal administration of OT_USH_101 was well tolerated in the low-dose treatment arm. OT_USH_101 treatment resulted in high expression of human USH1C_a1. Although histopathological changes were not severe, more frequent changes were observed in the high-dose group.

Repeated, High-dose Fentanyl Administration in Rats Reveals Minimal Tolerance to Unconsciousness, Bradycardia, Muscle Rigidity and Respiratory Depression.

Fentanyl is a synthetic opioid that is widely used in anesthesiology, but its illicit use is rapidly increasing. At high doses fentanyl induces unconsciousness and muscle rigidity, the mechanisms of which are poorly understood. Since animal models are needed to study these effects, the aim of this study was to establish a rat model of fentanyl abuse and investigate the effects of repeated high-dose fentanyl injections on loss of righting reflex, heart rate, respiratory depression, muscle, and brain activity. Male and female Sprague-Dawley rats were studied (n=40). A bolus of 100µg/kg fentanyl was administered intravenously twice a week for five consecutive weeks. Time to return of righting reflex (RORR) after fentanyl injection and changes in EMG/EEG activity as well as heart rate were analyzed. Additionally, arterial blood gas analysis for evaluation of ventilation was performed. Mixed-effect models with Dunnet's test and effect sizes were used for statistical analysis. Repeated injections resulted in a U-shaped change in time to RORR with the longest latency after the first exposure (median: 50[1st-3rd quartile:36-56]min) and the shortest after the fifth exposure (16[13-33]min). Following fentanyl administration, heart rate dropped immediately by 225[95%CI: 179, 271]bpm (F=3952.16, p<.001), while EMG activity increased by 291[95%CI: 212, 370]% (F=27.51, p<0.001) and PaCO2 inclined by 49.4[95%CI: 40.6, 58.2]mmHg (F=75.97, p<0.001) within 5 minutes after injection. Additionally, pH decreased by 0.48[95%CI: 0.41, 0.54] (F=142.00, p<0.01), and PaO2 decreased by 50.4[40.8, 60.0]mmHg (F=57.90, p<0.001). Repeated fentanyl exposures did not significantly affect the extent of these changes (EMG: F=1.63, p=0.237; PaCO2: F=1.23, p=0.312; HR: F=1.05, p=0.400; pH: F=3.05, p=0.066; pO2: F=3.35, p=0.052). EEG analysis revealed that repeated fentanyl exposures elicited significantly higher absolute power in frequencies >20Hz as indicated by an area under the receiver operator characteristics curve >0.7. We established a rodent model of repeated, high-dose fentanyl administration. Overall, significant evidence of tolerance was not observed after ten exposures of high-dose fentanyl for any of the analyzed parameters. These results suggest that tolerance does not develop for fentanyl-induced unconsciousness, muscle rigidity, or respiratory depression.

The Effect Of Erythropoietin Administration In Experimental Burns Wound Healing: An Animal Study

Background: The hematopoietic growth factor erythropoietin (EPO) attracts attention due to its all-tissue-protective pleiotropic properties. The purpose of this study is to investigate the effect of EPO in experimental burn wounds healing. Methods: Fifteen healthy Sprague-Dawley, strain of Rattus Novergicus weighing 300-350 grams, were prepared to achieve deep dermal burns. Animals were randomized to receive either low-dose EPO injection (600 IU/mL), high-dose EPO injection (3000 IU/mL) or nothing (control group). After 14 days of observations, quantitative and qualitative assessments of wound healing was determined. Results: The size of the wound area and re-epithelialization rate percentage was determined on Day-0, Day-5, Day-10, and Day-14. The average of raw surface areas measurement (p value: 0.012 in day-5; 0.009 in day-10 and 0.000 in day-14) and healing percentage of the lesions (p value: 0.011 in day-5; 0.016 in day-10 and 0.010 in day-14) were significantly best in the low-dose EPO grup compared to the control group and high-dose EPO grup. The histopathology evaluation revealed that the highest score for for re-epithelialization, granulation tissue and neo-angiogenesis were achieved by the low-dose EPO injection group than in both control and high-dose EPO injection groups. Conclusion: In this animal study using Sprague-Dawley rats, Recombinant Human EPO (rHuEPO) injection administration prompted the evidences of improved re-epithelialization and wound healing process of the skin caused by deep dermal burns. These findings may lead to a new therapeutic approach to improve the clinical outcomes for the management of burns wound healing.

Successful Treatment of Severe, Poorly Controlled Benign Essential Blepharospasm with DaxibotulinumtoxinA.

Benign essential blepharospasm is a focal dystonia characterized by involuntary contractions of the orbicularis oculi. Botulinum toxin type A injections are often first-line treatment, but patients may experience refractory symptoms or decreased response over time. DaxibotulinumtoxinA, a novel botulinum toxin type A product, has shown promise in cervical dystonia and facial rhytids but has not been previously reported for benign essential blepharospasm treatment. This case highlights a 57-year-old male with severe, poorly controlled benign essential blepharospasm despite high-dose injections of onabotulinumtoxinA and incobotulinumtoxinA. He subsequently received 100 units of daxibotulinumtoxinA in the same periorbital injection pattern with subjective faster onset, extended duration of effect, and improved symptom management compared to previous treatments. Notably, the patient experienced 50% to 75% efficacy retention at 3 months postinjection, significantly better than his response to other botulinum toxin type A products. This case suggests that daxibotulinumtoxinA may be an effective treatment for benign essential blepharospasm including patients experiencing poor symptom control with other botulinum toxin type A products.

Limited Experimental Susceptibility of Post-Smolt Atlantic salmon (Salmo salar) to an Emergent Strain of Vibrio Anguillarum Serotype O3

Preliminary evidence has showed an emergent serotype O3 (SO3) strain of Vibrio anguillarum to cause mortality in pre-smolt Atlantic salmon (Salmo salar) by injection with &gt;105 colony forming units (cfus). Here, we sought to identify the susceptibility of Atlantic salmon post-smolts to this emergent strain by both injection and cohabitation to better understand transmission risk within cultured salmon and possibly between salmon and Atlantic menhaden (Brevoortia tyrannus), where this strain was identified. We identified that although mortality could be induced with a high-dose (&gt;106 cfus) intraperitoneal injection of the emergent SO3 strain (cumulative mortality of 40%), post-smolt Atlantic salmon were highly refractory to a low dose (&lt;106 cfus; cumulative mortality of 3%) or cohabitation exposure (no mortality). A qPCR assay targeting this strain was developed and analytically validated, revealing the limited presence of bacterial DNA in the spleen of low-dose-injected fish (2/36) and no detections in sampled cohabitants (0/70) across three timepoints during the 27-day challenge. These results suggest that although Atlantic salmon can succumb to high-dose artificial infections with V. anguillarum SO3, the risk of natural transmissibility and susceptibility of Atlantic salmon to this emergent strain is anticipated to be low.

Electroacupuncture Promotes Gastric Motility by Suppressing Pyroptosis via NLRP3/Caspase-1/GSDMD Signaling Pathway in Diabetic Gastroparesis Rats.

To investigate the mechanism of electroacupuncture (EA) in treating diabetic gastroparesis (DGP) by inhibiting the activation of Nod-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome and pyroptosis mediated via NLRP3/cysteinyl aspartate specific proteinase-1 (caspase-1)/gasdermin D (GSDMD) signaling pathway. Forty Sprague-Dawley rats were randomly divided into 4 groups including the control, DGP model, EA, and MCC950 groups. The DGP model was established by a one-time high-dose intraperitoneal injection of 2% streptozotocin and a high-glucose and high-fat diet for 8 weeks. EA intervention was conducted at Zusanli (ST 36), Liangmen (ST 21) and Sanyinjiao (SP 6) with sparse-dense wave for 15 min, and was administered for 3 courses of 5 days. After intervention, the blood glucose, urine glucose, gastric emptying, and intestinal propulsive rate were observed. Besides, HE staining was used to observe histopathological changes in gastric antrum tissues, and TUNEL staining was utilized to detect DNA damage. Protein expression levels of NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), pro-caspase-1, caspase-1 and GSDMD were measured by Western blot. Immunofluorescence staining was employed to assess the activity of GSDMD-N. Lactate dehydrogenase (LDH) levels were detected by using a biochemical kit. DGP rats showed persistent hyperglycemia and a significant decrease in gastrointestinal motility (P<0.05 or P<0.01), accompanied by pathological damage in their gastric antrum tissues. Cellular DNA was obviously damaged, and the expressions of NLRP3, ASC, pro-caspase-1, caspase-1 and GSDMD proteins were significantly elevated, along with enhanced fluorescence signals of GSDMD-N and increased LDH release (P<0.01). EA mitigated hyperglycemia, improved gastrointestinal motility in DGP rats and alleviated their pathological injury (P<0.05). Furthermore, EA reduced cellular DNA damage, lowered the protein levels of NLRP3, ASC, pro-caspase-1, caspase-1 and GSDMD, suppressed GSDMD-N activity, and decreased LDH release (P<0.05 or P<0.01), demonstrating effects comparable to MCC950. EA promotes gastrointestinal motility and repairs the pathological damage in DGP rats, and its mechanism may be related to the inhibition of NLRP3 inflammasome and pyroptosis mediated by NLRP3/caspase-1/GSDMD pathway.

Restorative effects of melatonin on bisphenol a-induced interference of gene expression in hypothalamic pituitary axis following early exposure

Bisphenol-A is a standard monomer used in manufacturing plastics and epoxy resins, and it is widely used in food preservation and packaging. It is an endocrine-disrupting chemical miming the endogenous estradiol hormone. Melatonin regulates sleep-wake cycles and plays essential physiological roles in the body through its antioxidative properties. This research aims to ascertain the impact of Bisphenol A on the hypothalamic-pituitary-ovarian axis and determine melatonin's function on possible BPA-induced effects. Six adult male Wistar rats and 12 adult female Wistar rats of proven fertility were bred and organized into groups. These animals were subjected to subcutaneous injections of high and low doses of bisphenol A from postnatal days 0-3, then oral melatonin. The rats were allowed to mature into full-grown adults and euthanized at 120 ±4 days. The serum and hypothalamic-pituitary-ovarian tissues were collected for various assays. Compared to the control groups, groups administered varying doses of bisphenol A showed significant overexpression of estrogen and androgen receptors. Administration of Melatonin showed some reversal and reparative effects on damage of the hypothalamic pituitary ovarian axis. Elevated estrogen receptor levels induced by Bisphenol A altered receptor function. Melatonin showed some promising reparative effects.

Success Rate and Predicting Factors for Repeated High-Dose Intradetrusor Dysport Injections in Children With Neurogenic Bladder: A Retrospective Study.

Evaluating the effectiveness and safety of repeated high-dose intradetrusor abobotulinumtoxin A (Dysport®) injections for the treatment of pediatric neurogenic bladders refractory to medications. Retrospective interventional study. The cohort included 37 children (22 boys and 15 girls) of median age 9.2 years. Inclusion criteria were diagnosis of neurogenic bladder and failure to respond to medical treatment. Exclusion criteria were augmented bladder, insufficient data, and interval of > 11 months between video-urodynamic study and Dysport injection. All participants were treated with an intra-detrusor injection of Dysport 30 IU/kg (up to 1000 IU) under general anesthesia. Repeated (second and third) injections were scheduled (6-12 months) in patients who demonstrated an improvement in cystometric parameters. All participants underwent video urodynamic testing before onset of treatment and 4-5 months after subsequent injection. Success of treatment was defined as a decrease in end filling pressure (EFP) to < 40 cm H2O and/or a 20% increase in maximal cystometric capacity (MCC). These parameters along with initial bladder features were evaluated for ability to predict treatment success. No side effects of Dysport were observed or reported. The overall success rate was 62%. MCC increased by a median of 30% (IQR 200-300, p < 0.001), 37% (IQR 197-310, p = 0.001) and 45% (IQR 245-300, p = 0.025) after the first, second and third injections, respectively. Median EFP decreased from 45 cm H2O to 34 cm H2O (IQR 20-45, p = 0.029), 23 cm H2O (IQR 20-37, p = 0.004), and 20 cm H2O (IQR 12-32, p = 0.049) after the first, second, and third injections, respectively. No predicting factor of success of treatment were found; However, three of five cases of "end stage" bladder showed improvement. High-dose Dysport injection is safe and effective for the treatment of neurogenic bladder. Studies with larger cohort and a control group would further elucidate which bladders would benefit most. At present, we recommend treating also bladders with "end stage" features with botulinum toxin before considering augmentation.

Local, Sustained, and Targeted Co-Delivery of MEK Inhibitor and Doxorubicin Inhibits Tumor Progression in E-Cadherin-Positive Breast Cancer.

Effectively utilizing MEK inhibitors in the clinic remains challenging due to off-target toxicity and lack of predictive biomarkers. Recent findings propose E-cadherin, a breast cancer diagnostic indicator, as a predictor of MEK inhibitor success. To address MEK inhibitor toxicity, traditional methodologies have systemically delivered nanoparticles, which require frequent, high-dose injections. Here, we present a different approach, employing a thermosensitive, biodegradable hydrogel with functionalized liposomes for local, sustained release of MEK inhibitor PD0325901 and doxorubicin. The poly(δ-valerolactone-co-lactide)-b-poly(ethylene-glycol)-b-poly(δ-valerolactone-co-lactide) triblock co-polymer gels at physiological temperature and has an optimal degradation time in vivo. Liposomes were functionalized with PR_b, a biomimetic peptide targeting the α5β1 integrin receptor, which is overexpressed in E-cadherin-positive triple negative breast cancer (TNBC). In various TNBC models, the hydrogel-liposome system delivered via local injection reduced tumor progression and improved animal survival without toxic side effects. Our work presents the first demonstration of local, sustained delivery of MEK inhibitors to E-cadherin-positive tumors alongside traditional chemotherapeutics, offering a safe and promising therapeutic strategy.

A case of intravenous injection of mercury poisoning

There are few reports of poisoning caused by high-dose intravenous injection of mercury. Its clinical manifestations are diverse and the risk of mortality is high. Currently, the pathogenesis is not clear and the treatment experience is insufficient, leading to difficulties in clinical diagnosis and treatment. In this article, the data of a case of mercury poisoning caused by intravenous self-administration was analyzed and summarized. The patient developed multiple organ dysfunction syndrome after intravenous injection of high-dose mercury. After comprehensive treatment, such as mercury removal, organ support, and infection prevention, the condition was improved. This case suggests that intravenous injection of mercury can cause damage to the functions of multiple organs, such as the heart, lungs, and kidneys. Early treatment and intervention can bring benefits.

WITHDRAWN: Experimental study on improvement of lung injury in septic rats by inhibiting RIOK3-ferritin autophagy axis with Ginkgo biloba extract

IntroductionThis study aimed to explore the mechanism of Ginkgo biloba extract(GBE, 银杏叶提取物) improving lung injury in septic rats by interfering with ferritin autophagy. MethodsA rat model of sepsis was established by cecal puncture method, and the animals were randomly divided into 6 groups, including control group, sham operation group, model group and GBE low, medium and high concentration treatment groups. Groups GBE low, medium and high concentration were given intraperitoneal injection of low dose (10mg/kg), medium dose (20mg/kg) and high dose (40mg/kg) GBE, respectively. Detect relevant indicators. ResultsIt was found that the lung tissue of rats in the model group had obvious pathological damage, and the expression of ferritin (FTH1) was significantly reduced, the expression of ferritin autophagy-related factors such as RIOK3, NCOA4, and LC3B was significantly increased, and the contents of Fe2+, malondialdehyde (MDA), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and the lung/body weight ratios were significantly increased. GBE significantly improved the pathological damage of lung tissue in rats, increased the expression of FTH1, knocked down the expression of RIOK3, NCOA4 and LC3B, reduced the contents of Fe2+, MDA, IL-6, and TNF-α, and the lung/body weight ratios, especially in the medium-dose GBE group. ConclusionsGBE can down-regulate the expression of NCOA4 by inhibiting the expression of RIOK3, thereby inhibiting ferritin autophagy and ferroptosis, and ameliorating acute lung injury in sepsis rats. The best effect is found in medium concentration GBE (20mg/kg).

Patient-important outcomes in type 2 diabetes: The paradigm of the sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists.

The newfound knowledge in type 2 diabetes (T2D) during the past decade for the sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) is wealthy in favorable results for key patient-important outcomes including morbidity, mortality and health-related quality of life (HRQoL). The SGLT-2i and GLP-1RA offer cardiovascular and renal protection beyond their glucose lowering effect, reduce body weight and hypoglycemia and improve diabetes-related distress, physical function and HRQoL. Along with the fixed-ratio combinations of basal insulin/GLP-1RA, they make feasible a regimen simplification and de-escalation from high dose and multiple injections of insulin reducing treatment burden. Besides cardiorenal risk reduction, the SGLT-2i and GLP-1RA reduce the incidence of depression, cognitive decline, respiratory disease, gout, arrhythmias and other co-occurring conditions of T2D, namely multimorbidity, which frequently complicates T2D and adversely affects HRQoL. The alleviation of multimorbidity by the pleiotropic effects of the SGLT-2i and GLP-1RA, could improve patients' HRQoL. The use of the SGLT-2i and GLP-1RA should be increased within a shared decision-making in which they are reframed as cardiorenal risk-reducing medications with the potential to lower blood glucose. By improving outcomes that patients may highly perceive and value, the SGLT-2i and GLP-1RA may facilitate the contemporary person-centered management of T2D.

Chronic Edema Management of the Lower Extremities.

Peripheral edema is a prevalent condition affecting patients dealing with an assortment of health conditions, such as congestive heart failure (CHF), liver disease, venous insufficiency, and postoperative surgical complications. Edema can present in a variety of ways, ranging from mild localized symptoms to severely debilitating forms that impact patients' daily lives. Despite the vast number of publications addressing the underlying causes of peripheral edema, there seems to be an absence of literature that presents the effectiveness and compliance of current management techniques. This paper aims to condense the current literature on the effectiveness and compliance of current edema management approaches across various common etiologies, with the intentionof identifying alternative therapies that could enhance the quality of care for patients with chronic lower extremity edema. Several promising new therapies such as exogenous calf muscle stimulation, leg raise exercises, high-dose albumin injections, and device-based negative pressure lymph drainage (NPLD), deviate from the currentestablished standard of care. This scoping review revealed diverse treatment methods tailored to the specific underlying etiology of edema. The use of diuretics and vasodilators has shown benefits in treating CHF-induced edema but failed to alleviate and prevent the recurrence of edema in hospitalized and recently discharged patients. Albumin injections have emerged as a potential alternative treatment for edema due to liver disease, addressing hypoalbuminemia symptoms caused by liver failure. Patients with vascular causes of edema are efficaciously treated conservatively with compression stockings, although patient adherence remains a hurdle. For postoperative edema, device-based NPLD appears promising, with potential benefits over elastic bandage wraps and kinesiology taping.

Single high-dose intravenous injection of Wharton’s jelly-derived mesenchymal stem cell exerts protective effects in a rat model of metabolic syndrome

BackgroundMetabolic syndrome (MetS) is a significant epidemiological problem worldwide. It is a pre-morbid, chronic and low-grade inflammatory disorder that precedes many chronic diseases. Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) could be used to treat MetS because they express high regenerative capacity, strong immunomodulatory properties and allogeneic biocompatibility. This study aims to investigate WJ-MSCs as a therapy against MetS in a rat model.MethodsTwenty-four animals were fed with high-fat high-fructose (HFHF) diet ad libitum. After 16 weeks, the animals were randomised into treatment groups (n = 8/group) and received a single intravenous administration of vehicle, that is, 3 × 106 cells/kg or 10 × 106 cells/kg of WJ-MSCs. A healthy animal group (n = 6) fed with a normal diet received the same vehicle as the control (CTRL). All animals were periodically assessed (every 4 weeks) for physical measurements, serum biochemistry, glucose tolerance test, cardiovascular function test and whole-body composition. Post-euthanasia, organs were weighed and processed for histopathology. Serum was collected for C-reactive protein and inflammatory cytokine assay.ResultsThe results between HFHF-treated groups and healthy or HFHF-CTRL did not achieve statistical significance (α = 0.05). The effects of WJ-MSCs were masked by the manifestation of different disease subclusters and continuous supplementation of HFHF diet. Based on secondary analysis, WJ-MSCs had major implications in improving cardiopulmonary morbidities. The lungs, liver and heart show significantly better histopathology in the WJ-MSC-treated groups than in the untreated CTRL group. The cells produced a dose-dependent effect (high dose lasted until week 8) in preventing further metabolic decay in MetS animals.ConclusionsThe establishment of safety and therapeutic proof-of-concept encourages further studies by improving the current therapeutic model.

"Hurts less, lasts longer"; a qualitative study on experiences of young people receiving high-dose subcutaneous injections of benzathine penicillin G to prevent rheumatic heart disease in New Zealand.

Four-weekly intramuscular (IM) benzathine penicillin G (BPG) injections to prevent acute rheumatic fever (ARF) progression have remained unchanged since 1955. A Phase-I trial in healthy volunteers demonstrated the safety and tolerability of high-dose subcutaneous infusions of BPG which resulted in a much longer effective penicillin exposure, and fewer injections. Here we describe the experiences of young people living with ARF participating in a Phase-II trial of SubCutaneous Injections of BPG (SCIP). Participants (n = 20) attended a clinic in Wellington, New Zealand (NZ). After a physical examination, participants received 2% lignocaine followed by 13.8mL to 20.7mL of BPG (Bicillin-LA®; determined by weight), into the abdominal subcutaneous tissue. A Kaupapa Māori consistent methodology was used to explore experiences of SCIP, through semi-structured interviews and observations taken during/after the injection, and on days 28 and 70. All interviews were recorded, transcribed verbatim, and thematically analysed. Low levels of pain were reported on needle insertion, during and following the injection. Some participants experienced discomfort and bruising on days one and two post dose; however, the pain was reported to be less severe than their usual IM BPG. Participants were 'relieved' to only need injections quarterly and the majority (95%) reported a preference for SCIP over IM BPG. Participants preferred SCIP over their usual regimen, reporting less pain and a preference for the longer time gap between treatments. Recommending SCIP as standard of care for most patients needing long-term prophylaxis has the potential to transform secondary prophylaxis of ARF/RHD in NZ and globally.

Effect of high-dose intravenous iron injection on hepatic function in a rat model of cirrhosis.

To investigate the hepatic effects of high-dose intravenous (IV) iron, including those on liver function and the degree of fibrosis, in a rat model of cirrhosis. We evenly allocated 25 Sprague-Dawley rats into five groups: normal rats (control group), cirrhotic rats receiving IV normal saline (liver cirrhosis [LC] group), and cirrhotic rats receiving 20, 40, or 80 mg/kg IV ferric carboxymaltose (LC-iron20, LC-iron40, and LC-iron80 group, respectively). Biochemical parameters were compared at 0, 7, 14, 21, and 28 days. The degrees of hepatic fibrosis and iron deposition were evaluated. Inflammatory and oxidative stress markers were also compared. There were no significant differences in the 28-day serum alanine aminotransferase levels among the LC-iron20, LC-iron40, and LC-iron80 groups (69 ± 7, 1003 ± 127, 1064 ± 309, 919 ± 346, and 820 ± 195 IU/L in the control, LC, LC-iron20, LC-iron40, and LC-iron80 groups, respectively). Hepatic iron accumulation increased in a dose-dependent manner, but the degree of hepatic fibrosis was comparable among the groups. The inflammatory and oxidative stress marker levels did not differ significantly according to the IV iron dose. Administration of IV iron at various high doses appears safe in our rat model of cirrhosis.

The Efficacy of Botulinum Toxin A Injection for Gastrocnemius Hypertrophy: A Prospective, Randomized, Double-blinded Controlled Trial

Background: Many individuals hold an interest in aesthetic appeal, with one aspect of physical attractiveness being the alluring contour of the lower leg. Utilizing botulinum toxin A (BTX-A) injections offers several advantages, including a short procedure time, low pain, and a speedy recovery. With a demand for high-level evidence regarding the effectiveness of BTX-A injections for correction of lower leg contour, we evaluated the safety and efficacy of BTX-A injection for improvement of gastrocnemius muscle hypertrophy. Methods: We conducted a prospective, randomized, and controlled clinical trial to evaluate whether the injection of BTX-A into the gastrocnemius muscle could decrease muscular hypertrophy. The patients were randomized into a low-dose injection (60 units) group and a high-dose injection group (100 units) for each leg. Demographics, clinical outcome, and satisfaction score were compared between the two groups. Results: A total of 20 patients and 40 legs were enrolled in this study. Clinical and surgical demographics were similar between the two groups. BTX-A injection showed a significant decrease in the circumference of the calf after 8 weeks (preinjection: 36.35 ± 0.63 cm versus postinjection: 35.87 ± 0.61 cm; P = 0.03). However, no significant difference was observed between the low- and the high-dose group (−0.52 ± 0.74 cm versus −0.44 ± 1.04 cm, P = 0.78). Conclusions: BTX-A injection can be a good noninvasive method for the correction of hypertrophic gastrocnemius muscles. This study supports the use of BTX-A injections in patients unsatisfied with lower leg hypertrophy.

STING-Pathway Inhibiting Nanoparticles (SPINs) as a Platform for Treatment of Inflammatory Diseases.

Aberrant activation of the cyclic GMP-AMP synthase (cGAS)/Stimulator of Interferon Genes (STING) pathway has been implicated in the development and progression of a myriad of inflammatory diseases including colitis, nonalcoholic steatohepatitis, amyotrophic lateral sclerosis (ALS), and age-related macular degeneration. Thus, STING pathway inhibitors could have therapeutic application in many of these inflammatory conditions. The cGAS inhibitor RU.521 and the STING inhibitor H-151 have shown promise as therapeutics in mouse models of colitis, ALS, and more. However, these agents require frequent high-dose intraperitoneal injections, which may limit translatability. Furthermore, long-term use of systemically administered cGAS/STING inhibitors may leave patients vulnerable to viral infections and cancer. Thus, localized or targeted inhibition of the cGAS/STING pathway may be an attractive, broadly applicable treatment for a variety of STING pathway-driven ailments. Here we describe STING-Pathway Inhibiting Nanoparticles (SPINS)-poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with RU.521 and H-151-as a platform for enhanced and sustained inhibition of cGAS/STING signaling. We demonstrate that SPINs are equally or more effective at inhibiting type-I interferon responses induced by cytosolic DNA than free H-151 or RU.521. Additionally, we describe a SPIN formulation in which PLGA is coemulsified with poly(benzoyloxypropyl methacrylamide) (P(HPMA-Bz)), which significantly improves drug loading and allows for tunable release of H-151 over a period of days to over a week by varying P(HPMA-Bz) content. Finally, we find that all SPIN formulations were as potent or more potent in inhibiting cGAS/STING signaling in primary murine macrophages, resulting in decreased expression of inflammatory M1-like macrophage markers. Therefore, our study provides an in vitro proof-of-concept for nanoparticle delivery of STING pathway inhibitors and positions SPINs as a potential platform for slowing or reversing the onset or progression of cGAS/STING-driven inflammatory conditions.

Exploring the Tumor-Associated Risk of Mesenchymal Stem Cell Therapy in Veterinary Medicine.

Mesenchymal stem cell (MSC) therapy has been actively applied in veterinary regenerative medicine to treat various canine and feline diseases. With increasing emphasis on safe cell-based therapies, evaluations of their tumorigenic potential are in great demand. However, a direct confirmation of whether tumors originate from stem cells or host cells is not easily achievable. Additionally, previous studies evaluating injections of high doses of MSCs into nude mice did not demonstrate tumor formation. Recent research focused on optimizing MSC-based therapies for veterinary patients, such as MSC-derived extracellular vesicles in treating different diseases. This progress also signifies a broader shift towards personalized veterinary medicine, where treatments can be tailored to individual pets based on their unique genetic profiles. These findings related to different treatments using MSCs emphasize their future potential for veterinary clinical applications. In summary, because of lower tumor-associated risk of MSCs as compared to embryonic and induced pluripotent stem cells, MSCs are considered a suitable source for treating various canine and feline diseases.