Administration Of Saline Research Articles

Comparative induction of benign prostate hyperplasia using testosterone propionate and estradiol benzoate in rabbit model

Benign prostatic hyperplasia (BPH) is a common non-cancerous enlargement of the prostate that usually occurs in aging men and some higher mammals. Many studies have been conducted to explore different treatment strategies for managing BPH. However, a suitable animal model for studying BPH is necessary. So far, only a few animal models, such as rat and dog models, have been used for this purpose. This study aimed to compare the assessment of the BPH model induced in rabbits through the administration of exogenous testosterone and estrogen post-bilateral orchidectomy. Fifteen (N=15) indigenous Nigerian rabbits were used for this experiment. The rabbits were orchiectomized and randomly divided into 3 groups: the testosterone, estrogen, and control groups. Seven days after bilateral orchidectomy, BPH was induced using exogenous subcutaneous administration of testosterone (15 mg kg-1), estrogen (0.75 mg kg-1), and normal saline (1 mL) for 4 weeks. After completion of the treatments, prostates were removed. The weight, volume, prostate index, and histologic scoring were determined. There were significant changes (p<0.05) in prostate weight, volume, and index. Testosterone and estrogen-treated groups differed significantly from the control groups. There were no significant differences in all the parameters between the testosterone and the estrogen groups. Histological evaluation revealed hyperplasia of the epithelium of the prostate gland and increased stromal connective tissues with a corresponding increase in the number of glandular units with secretory-filled fluid within the lumens of the glands. The benign prostate hyperplasia rabbit model was developed successfully using exogenous treatment with testosterone propionate. Testosterone appeared to have significant roles in the development of prostate hyperplasia when compared to estrogen.

Differential effects of chronic and intermittent administration of taurine on alcohol binge drinking in male rats

Episodic consumption of high doses of alcohol in a short period (binge drinking - BD) among adolescents is known to be harmful to their brain development. Chronic use of taurine increases voluntary alcohol consumption and shows an anxiolytic-like effect in rats. In this study, we evaluated the differential effects of chronic and intermittent taurine administration on alcohol consumption and behavioral changes in adolescent and young adult rats subjected to the BD model. Male Wistar rats (35 days old) were divided into 4 groups for daily intraperitoneal administration of saline (SAL); taurine, 100 mg/kg (TAU); taurine on BD days and saline on intervals (TAU/SAL); and saline on BD days and taurine on intervals (SAL/TAU). They were exposed to 4 cycles of BD, with free access to alcoholic solution (20 % w/v), for 2 h, 3 days per week. At the end of the 3rd cycle, anxiety-like behaviors were assessed using the light-dark task. After euthanasia, plasma and prefrontal cortex samples were collected to measure corticosterone and BDNF levels, respectively. Chronic taurine treatment did not alter alcohol consumption in rats, whereas intermittent administration increased alcohol intake after 4 BD exposures (TAU/SAL: +19.4 % and SAL/TAU: +21.6 %). No anxiolytic-like effects were found by taurine administration, nor were there changes in serum corticosterone or BDNF levels in the frontal cortex of young adult rats. Intermittent taurine, but not chronic treatment, increased alcohol intake among rats after the second week of exposure. The translation of these results to humans is concerning since the combination of alcohol and drinks containing taurine is common among adolescent and young adult individuals.

Spindles in WAG/Rij Rats with Absence Epilepsy and Comorbid Depression

WAG/Rij rats are a valid model of absence epilepsy and comorbid depression. We have previously shown that WAG/Rij rats have disturbances in the sleep-wake cycle and changes in the characteristics of sleep spindles. A negative correlation was also found between the number of spike-wave discharges (SWD) and the duration of rapid eye movement (REM) sleep. Clinical evidence suggests that the traditional antidepressants imipramine and fluoxetine are effective in suppressing symptoms of depression, but may have a negative impact on the sleep-wake cycle and comorbid epilepsy in patients. Our previous studies in WAG/Rij rats showed that imipramine, when administered chronically, increases the number of SWDs, while fluoxetine at the same dose reduces their number, although both antidepressants have a pronounced antidepressant effect. Comparison of the effects of the antidepressants imipramine and fluoxetine on the sleep-wake cycle and sleep spindles in WAG/Rij rats remains unstudied. The purpose of this work is to find out: 1) what effects do imipramine and fluoxetine have on the sleep-wake cycle and the characteristics of sleep spindles in WAG/Rij rats and 2) whether there are differences in their effects. To achieve this goal, the characteristics of the sleep-wake cycle and sleep spindles were compared in WAG/Rij rats after chronic administration of antidepressants and saline and in non-epileptic Wistar rats. Administration of imipramine led to a significant decrease in the duration of REM sleep. The administration of imipramine, compared with fluoxetine, also increased the latency of the transition to sleep and the transition to REM sleep. Sleep spindle amplitude was significantly increased by both antidepressants. However, the spectral power density of “slow” and “medium” spindles, which predominate in WAG/Rij rats compared to Wistar rats, was significantly higher after administration of imipramine than fluoxetine. The results suggest that imipramine causes greater negative changes in the sleep-wake cycle and sleep spindles than fluoxetine. Studies in the WAG/Rij rat model indicate that fluoxetine is more preferable antidepressant for the treatment of depressive disorders comorbid with absence epilepsy, since it does not cause a significant deterioration in sleep quality. These results are consistent with clinical data.

No Benefit of 3% Hypertonic Saline Following Experimental Intracerebral Hemorrhage

Intracerebral hemorrhage (ICH) is a stroke subtype with a high mortality rate (~ 40%). After ICH, the mass effect of the hematoma and edema contribute to raised intracranial pressure (ICP) and poor outcome. Endogenous compensatory mechanisms that blunt ICP elevations include redirection of venous blood and cerebrospinal fluid, along with brain tissue compliance (e.g., decreased cell volume, increased cell density); however, these limited reserves can be exhausted after severe stroke, resulting in decompensated ICP that requires careful clinical management. Management strategies can include administration of hypertonic saline (HTS), an osmotic agent that putatively attenuates edema, and thereby ICP elevations. Evidence regarding the efficacy of HTS treatment following ICH remains limited. In this study, adult male rats were given a collagenase-induced striatal ICH and a bolus of either 3% HTS or 0.9% saline vehicle at 2- and 14-hours post-stroke onset. Neurological deficits, edema, ipsilateral cell volume and density (in areas S1 and CA1), and contralateral CA1 ultrastructural morphology were assessed 24 h post-ICH. Animals had large bleeds (median 108.2 µL), extensive edema (median 83.9% brain water content in ipsilateral striatum), and evident behavioural deficits (median 5.4 neurological deficit scale score). However, HTS did not affect edema (p ≥ 0.4797), behaviour (p = 0.6479), cell volume (p ≥ 0.1079), or cell density (p ≥ 0.0983). Qualitative ultrastructural assessment of contralateral area CA1 suggested that HTS administration was associated with paradoxical cellular swelling in ICH animals. Overall, there was no benefit with administering 3% HTS after ICH.

Clinically relevant findings on 24-h head CT after acute stroke therapy: The 24-h CT score.

Routine head computed tomography (CT) is performed 24 h post-acute stroke thrombolysis and thrombectomy, even in patients with stable or improving clinical deficits. Predicting CT results that impact management could help prioritize patients at risk and potentially reduce unnecessary imaging. In this institutional review board (IRB)-approved retrospective study, data from 1461 consecutive acute ischemic stroke patients at our Comprehensive Stroke Center (n = 8943, 2012-2022) who received intravenous thrombolysis or endovascular therapy, exhibited stable or improving 24-h exams, and underwent 24-h follow-up head CT per standard acute stroke care guidelines. CT reports 24 h post-stroke were reviewed for edema, mass effect, herniation, and hemorrhage. The primary outcome was any clinically relevant 24-h CT finding that led to changes in antithrombotic treatment or blood pressure goals, extended intensive care unit (ICU) stays or hospitalizations, neurosurgical interventions, or administration of mannitol or hypertonic saline. Multivariable logistic regression identified independent predictors of clinically meaningful CT abnormalities. A 24-h CT score was developed and cross-validated. The mean age was 70 years, with 47% women. The median National Institutes of Health Stroke Scale (NIHSS) score at admission was 12 (interquartile range (IQR): 6-18). Stroke-related abnormalities on 24-h CT were present in 325 patients (22.2%), with 183 (12.5%) showing clinically relevant findings. Age, admission NIHSS, and blood glucose levels were independent predictors of clinically relevant 24-h CT findings. The final model C statistic was 0.72 (95% confidence interval (CI): 0.68-0.76) in the derivation cohort and 0.72 (95% CI: 0.67-0.75) in bootstrapping validation. The 24-h CT score was developed using these predictors: NIHSS score 5-15 (+3); NIHSS score ⩾16 (+5); age < 75 years (+1); admission glucose ⩾ 140 mg/dL (+1). The prevalence of clinically relevant CT findings was 4.3% in the low-risk group (24-h CT score ⩽ 4), 11.3% in the medium-risk group (score 5), and 21.4% in the high-risk group (score ⩾ 6). The 24-h CT score demonstrated good calibration. In patients undergoing thrombolysis or thrombectomy who undergo routine 24-h head CT despite remaining clinically stable or improving, only one in eight prove to have 24-h head CT findings that impact management. The 24-h CT score provides risk stratification that may improve resource utilization. A.S. and B.Z. have full access to the data used in the analysis in this article. Deidentified data will be shared after ethics approval if requested by other investigators for purposes of replicating the results.

Effect of maneuvers, diuresis, and fluid administration on ultrasound-measured liver stiffness after Fontan.

To determine the effect of stress maneuvers/interventions on ultrasound liver stiffness measurements (LSMs) in patients with Fontan circulation and healthy controls. In this prospective, IRB-approved study of 10 patients after Fontan palliation and 10 healthy controls, ultrasound 2D shear-wave elastography LSMs were acquired at baseline and after maximum inspiration, expiration, standing, handgrip, aerobic exercise, i.v. fluid (500mL normal saline) administration, and i.v. furosemide (20mg) administration. Absolute and percent change in LSM were compared between baseline and each maneuver, and then from fluid infusion to after diuresis. Median ages were 25.5 and 26 years in the post-Fontan and control groups (p = 0.796). LSMs after Fontan were higher at baseline (2.6 vs. 1.3m/s) and with all maneuvers compared to controls (all p < 0.001). Changes in LSM with maneuvers, exercise, fluid, or diuresis were not significant when compared to baseline in post-Fontan patients. LSM in controls increased with inspiration (+0.02m/s, 1.6%, p = 0.03), standing (+0.07m/s, 5.5%, p = 0.03), and fluid administration (+0.10m/s, 7.8%, p = 0.002), and decreased 60 minutes after diuretic administration (-0.05m/s, -3.9%, p = 0.01) compared to baseline. LSM after diuretic administration significantly decreased when compared to after i.v. fluid administration at 30 minutes (-0.79m/s, -26.5%, p = 0.004) and 60 minutes (-0.78m/s, -26.2%, p = 0.017) for patients after Fontan and controls at 15 minutes (-0.12m/s, -8.70%, p = 0.002), 30 minutes (-0.15m/s, -10.9%, p = 0.003), and 60 minutes (-0.1m/s, -10.9%, p = 0.005). LSM after Fontan is higher with more variability compared to controls. Diuresis is associated with significantly decreased liver stiffness in both patients after Fontan and controls, with the suggestion of a greater effect in Fontan patients.

Effects of vitamin K2 administration on guided bone regeneration in diabetic rats.

The present study aimed to investigate the histomorphometric and immunohistochemical impacts of vitamin K2 on guided bone regeneration (GBR) in calvarial critical-size defects (CSDs) in diabetic rats. A total of 30 rats were used in this study, comprising 12 non-diabetic (control) rats and 18 with streptozotocin-nicotinamide-induced experimental Diabetes mellitus (DM). In all rats, two calvarial CSDs were created: one defect was left empty (E), the other was treated with bovine-derived bone graft and collagen-based resorbable membrane (GM). Study groups were as follows: control rats administered saline (n = 6, C-E and C-GM groups) or vitamin K2 (n = 6, CK-E and CK-GM groups) and diabetic rats administered saline (n = 6, DM-E and DM-GM groups) or vitamin K2 (n = 6, DMK-E and DMK-GM groups). After 4 weeks of saline or vitamin K2 administration, the rats were euthanized. Bone defect healing and new bone formation were assessed histomorphometrically, and osteocalcin and osteopontin levels were examined immunohistochemically. Percentage of new bone formation was greater in CK-GM vs. CK-E and in DMK-GM vs. DMK-E [d = 3.86 (95% CI = 16.38-28.61), d = 1.86, (95% CI = 10.74-38.58), respectively, p < .05]. Bone defect healing scores were higher in CK-GM vs. CK-E and in DMK-GM vs. DMK-E [d = 2.69 (95% CI = -2.12 to -0.87), d = 3.28 (95% CI = 0.98-1.91), respectively, p < .05]. Osteocalcin expression levels were elevated in CK-GM vs. CK-E, in DMK-GM vs. DMK-E [d = 1.19 (95% CI = 0.08-1.41), d = 1.10 (95% CI = 0.02-1.22), respectively p < .05]. Vitamin K2 enhanced osteocalcin expression levels in DMK-E vs. DM-E [d = 2.78, (95% CI = 0.56-1.53), p < .05] and in DMK-GM vs. DM-GM [d = 2.43, (95% CI = 0.65-2.10), p < .05]. Osteopontin expression was enhanced in defects treated with GM vs. E defects [C-GM vs. C-E, d = 1.56 (95% CI = 0.38-2.01); CK-GM vs. CK-E, d = 1.91 (95% CI = 0.49-1.72); DM-GM vs. DM-E, d = 2.34 (95% CI = -1.12 to -0.50); DMK-GM vs. DMK-E, d = 2.00 (95% CI = 0.58-1.91), p < .05]. The research findings suggest that administering vitamin K2 in GBR for rats with DM favorably impacts bone healing in CSDs, presenting an adjunctive strategy for bone regeneration.

Confirmation of epidural anesthesia with bupivakain in cats by ınfrared thermographic ımaging and SEP

In this study, the usability of electromyelography and infrared thermography was tested to confirm the success of epidural anesthesia. The cats were randomly divided into 2 groups as experimental and control groups. Cats were intubated and placed under inhalation anesthesia in the anesthesia device. SEP recordings were obtained from L7-S1, L6-L7, L6-L5 and L5-L4 intervals before epidural injection. Before epidural injection, infrared thermographic images and rectal temperature were taken from a distance of 50 cm where the areas where surface temperatures were to be measured were clearly visible. Following asepsis and antisepsis, 0.5% bupivacaine in the experimental group and saline in the control group were injected from the lumbosacral region. Infrared thermograms and rectal temperature were taken from each cat 7 times (0.min, 5.min, 10.min, 15.min, 20.min, 25.min and 30.min) for 30 minutes at 5 min intervals after injection. After the last infrared thermogram was recorded, post-epidural SEP was recorded. Rectal temperature values decreased gradually in all cats throughout the anesthesia period and no difference was observed between the groups. A decrease in potential duration and an increase in latency values were recorded in 10 cats with epidural 0.5% bupivacaine administration compared to 10 cats with epidural saline administration. Although there were only statistically significant values the amplitude values were not found to be kinetically significant. No clinically or statistically significant difference was observed in the infrared thermograms taken before epidural injection and 5 minutes after epidural injection in both groups.

Alcohol and fear conditioning produce strain-specific changes in the dorsal hippocampal transcriptome of adolescent C57BL/6J and DBA/2J mice.

Adolescent sensitivity to alcohol is influenced by genetic background. Data from our laboratory suggested that adolescent C57BL/6J and DBA/2J inbred mice differed in susceptibility to alcohol-induced deficits in dorsal hippocampus-dependent contextual fear learning. To investigate the biological underpinnings of this strain difference, we examined dorsal hippocampus gene expression using RNA-sequencing after alcohol or saline administration followed by Pavlovian fear conditioning across male and female C57BL/6J and DBA/2J adolescents. Strains exhibited dramatic differences in dorsal hippocampus gene expression. Specifically, C57BL/6J and DBA/2J strains differed by 3526 transcripts in males and 2675 transcripts in females. We identified pathways likely to be involved in mediating alcohol's effects on learning, including networks associated with Chrna7, a gene encoding the nicotinic cholinergic receptor alpha 7 subunit, and Fmr1, a gene encoding the fragile X messenger ribonucleoprotein. These findings provide insight into the mechanisms underlying strain differences in alcohol's effects on learning and suggest that different biological networks are recruited for learning based on genetics, sex, and alcohol exposure.

Chronic nasal inflammation early in life induces transient and long-term dysbiosis of gut microbiota in mice

The gut microbiota begins to colonize the host body following birth, develops during the suckling period and changes to the adult type after weaning. The early gut microbiota during the suckling period is thought to have profound effects on the host physiology throughout life but it is still unclear whether early dysbiosis is retained lifelong. Our previous study indicated that chronic nasal inflammation induces dysbiosis of gut microbiota in adult mice. In the present study, we addressed the question as to whether early exposure to chronic nasal inflammation induces dysbiosis, and if so, whether the dysbiosis is retained until adulthood and the sex differences in this effect. Male and female mice received repeated intranasal administration of lipopolysaccharide (LPS) or saline twice a week from P7 to P24 and were weaned at P24. The cecal contents were obtained for 16S rRNA analysis at 2 time points: at 4 weeks (wks), just after weaning, and at maturation to adulthood at 10 wks. The body weight did not differ between saline- and LPS-treated mice till around weaning, suggesting that the mothers’ milk was given similarly to all mice. At 4 wks, the beta diversity was significantly different between saline- and LPS-treated male and female mice and the composition of the gut microbiota changed in LPS-treated mice. The abundance of phylum Bacteroidota tended to decrease and that of Firmicutes increased in LPS-treated male mice, while the abundance of Deferribacterota increased in LPS-treated female mice. At 10 wks, the beta diversity was not different between saline- and LPS-treated mice, but the abundance of family Lachnospiraceae significantly decreased in LPS-treated male and female mice by LEfSe analysis. Together, chronic nasal inflammation early in life caused transient and long-term dysbiosis of gut microbiota, which may contribute to the onset and progress of metabolic and neuropsychiatric disorders.

Dexamethasone administration restored growth in dairy calves exposed to heat stress

Recent evidence indicates that the heat stress loss on the growth performance of calves is associated with the diversion of nutrients to control enteritis and systemic inflammation. In this study, we investigated the impact of heat stress on markers of inflammation, feed use-efficiency, and growth of dairy calves. We hypothesized that dexamethasone, which is known for its immunosuppressive and anti-inflammatory properties, would reduce inflammation and restore the growth of calves exposed to heat stress. Thirty-two Holstein bull calves (body weight (BW) 68.5 ± 1.37 kg; age 3.5 ± 0.5-week-old; mean ± SD) were housed in individual pens in climate-controlled rooms at constant ambient temperature and allowed to adjust to facilities for 5 d before the start of treatments. Calves were randomly assigned to one of 4 treatments (n = 8/treatment) in a 2 × 2 factorial arrangement of environment (ENV, thermoneutral or heat stress) and intervention (INT, saline or dexamethasone) imposed for 5 d as follow: 1) thermoneutral (constant ambient temperature of 20°C 24 h/d) and administration of saline, 2) thermoneutral (constant ambient temperature of 20°C 24 h/d) and administration of dexamethasone, 3) cyclic heat stress (40°C ambient temperature, from 0800 to 1900 h/d) and administration of saline, 4) cyclic heat stress (40°C ambient temperature, from 0800 to 1900 h/d) and administration of dexamethasone. Dexamethasone (0.05 mg/kg BW), or saline (1.2 mL) was administered intramuscularly on d 1 and 3. Upon completion of treatments, calves were euthanized on d 5 to obtain jejunum mucosa samples. Commercial milk replacer, starter grain, and water were offered, and intake was monitored daily. Rectal temperature and respiratory rate were monitored 3 times daily. Blood samples were collected on d 1, 3, and 5 to determine serum pro-inflammatory cytokine concentrations. A section of the jejunum was collected and snap-frozen to determine the concentration of pro-inflammatory markers. Statistical analyses included a mixed model, fixed effects of ENV, INT, consecutive measurements taken over time (d, h, or both), replica, and random effects of calf and error (SAS version 9.4, SAS Institute Inc., Cary, NC). The measurements collected immediately before treatment allocation were included as covariates in the model. An ENV effect showed that heat stress increased rectal temperature (38.72 vs. 39.21°C), respiratory rate (36 vs. 108 breaths/min), and water intake (3.2 vs. 6.6 L/d). The treatments did not affect dry matter intake. An ENV × INT interaction showed that heat stress with saline decreased average daily gain (ADG) by 35% and tended to decrease feed use-efficiency by 36%, but the use of dexamethasone to treat heat stress restored ADG and feed use-efficiency comparable to their basal levels. An ENV × INT interaction revealed that heat stress with saline increased jejunal interleukin (IL)-6 concentration 2-fold, but dexamethasone treatment of heat stress restored jejunal IL-6 concentration to basal levels. The bioenergetic cost of the heat stress-immune pro-inflammatory response ranged between 1.18 and 1.50 Mcal of ME. Overall, the administration of dexamethasone reduced the jejunal concentration of a pro-inflammatory marker and restored the heat stress-associated reduction in growth and feed use-efficiency. The immunomodulation and anti-inflammatory effects of dexamethasone could be part of a homeorhetic change that results in a shift from maintenance functions to support growth on calves exposed to heat stress.

Antibacterial and therapeutic effects of low energy shock waves on uropathogenic E. coli investigated by in vitro and in vivo cystitis rat model.

Low-energy shock waves (LESWs) are known to alter cell-membrane permeability. This study aimed to investigate the effect of LESWs on Escherichia coli and E. coli-induced cystitis in rats. Standardized suspensions of E. coli ATCC25922 were treated with or without LESWs (100 or 300 pulses; 0.12mJ/mm2; 2pulses/s) followed by bacterial counting, an antibiotic sensitivity test, and gene ontology analysis and gene-set enrichment analysis. Intravesical administration of saline or E. coli (0.5mL with 108CFU/mL) for 30min was performed in female Sprague-Dawley rats. The rats were treated with or without LESWs (300 pulses; 0.12mJ/mm2; 2pulses/s) on days 4 and 5. The changes in inflammatory reactions, uroplakin IIIa staining, and correlation with urodynamic findings were assessed on day 8. LESW treatment induced a decrease in CFU and the autoaggregation rate and increased the inhibition zone sizes in a cefazolin-sensitivity study. These changes were associated with gene expression in regulation of cellular membrane components, biofilm formation, and the ATP-binding cassette transporter pathway. E. coli induced bladder hyperactivity and an inflammatory reaction as well as decreased uroplakin IIIa staining; these effects were partially reversed by LESW treatment. The LESW antibacterial effect occurs by altering bacterial cell-membrane gene expression, enhancing antibiotic sensitivity, and inhibiting bladder inflammatory reaction and overactivity. These findings support the potential benefits of LESWs for treatment of recurrent or refractory bacterial cystitis.

Pulsatile Right Ventricle to Pulmonary Artery Extracorporeal Membrane Oxygenation in a Pigs

Background: We investigated the impact of right ventricle to pulmonary artery extracorporeal membrane oxygenation in acute respiratory dysfunction with or without pulsatile flow. Methods: We used bronchoalveolar lavage with intrapulmonary administration of warm saline to establish a severe acute respiratory distress syndrome model (ratio of partial pressure of oxygen in arterial blood to the fraction of inspiratory oxygen concentration ratio &lt;200) in eight piglets (mean body weight: 8.45±1.24 kg). The piglets were categorized into the pulsatile (N=4) and non-pulsatile extracorporeal membrane oxygenation groups (N=4). We started right ventricle to pulmonary artery extracorporeal membrane oxygenation with a 60 mL/kg/min flow to support the animals for 6 hours. We monitored hemodynamic data and blood gas levels for assessing base excess, and performed arterial blood sampling and electrocardiogram. Interleukin-6 and endotherlin-1 concentrations in blood plasma were evaluated before and after right ventricle to pulmonary artery extracorporeal membrane oxygenation. We compared the lung wet/dry weight ratio as a measure of pulmonary edema and collected lung tissue samples for the pathologically evaluating pneumocytes before and after right ventricle to pulmonary artery extracorporeal membrane oxygenation. Results: We maintained stable hemodynamics and extracorporeal membrane oxygenation flow above an arterial oxygen saturation of 85% in both groups. Pneumocyte evaluation showed clearly less pulmonary edema, pulmonary fibrosis, and inflammation. Interleukin-6 concentration was less in the pulsatile group than in the non-pulsatile group. Conclusions: Pulsatile right ventricle to pulmonary artery extracorporeal membrane oxygenation was less vasoconstrictive and maintained more effective oxygenated pulmonary flow. It ameliorates pulmonary circulation and facilitates recovery from acute respiratory failure.

Pharmacokinetic study of local and systemic gentamicin concentrations after subcutaneous implantation of a gentamicin-impregnated collagen sponge in dogs

This study evaluated the pharmacokinetics of commercial gentamicin-impregnated collagen sponges (GICS) applied subcutaneously in dogs. In six healthy beagles, an 11 ×6 cm subcutaneous pocket was created, a folded 10×10 cm GICS was inserted, and saline was injected to mimic a seroma. Wound fluid samples were aspirated, and the gentamicin concentration was determined. Simultaneously, blood samples were collected to evaluate the corresponding systemic gentamicin concentration. All samples were collected before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96, 120, and 168 hours after GICS placement. The local Cmax of gentamicin was reached after 0.5 hours (range, 0.5–1.0 hours) post-implantation in 5/6 dogs at a median concentration of 2053.3 µg/mL (range, 918.0–2791.9 µg/mL). Whitin 24 hours, the local concentration dropped below the MIC for Staphylococcus sp. (4 µg/mL) in 5/6 dogs. Plasma Cmax was achieved at a median of 1.2 hours post-implantation (range, 1.0–2.0 hours) and reached a median concentration of 10.3 µg/mL (range, 8.8–18.03 µg/mL). After 6 hours, the gentamicin concentration in the plasma was below 4 µg/mL in all dogs. The GICS provided a high local concentration of gentamicin in a short time with a local Cmax:MIC ratio of 513:1, largely sufficient to eliminate susceptible bacteria, including methicillin-resistant Staphylococcus pseudintermedius (MRSP) and Pseudomonas sp., in a clinical setting. The repeated administration of saline in the present study seemed to have induced a quicker gentamicin release from the GICS than described in previous studies that typically dealt with "drier" wounds.

Heparin-binding epidermal growth factor-like growth factor improves erectile function in streptozotocin-induced diabetic mice.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) serves as a pro-angiogenic factor; however, there is to our knowledge currently no reported research on the relationship between HB-EGF and diabetic erectile dysfunction (ED). In this study we aimed to determine whether HB-EGF can improve the erectile function of streptozotocin-induced diabetic mice and to explore the related mechanisms. Eight-week-old male C57BL/6 mice were used for diabetes induction. Diabetes mellitus (DM) was induced by low-dose injections of streptozotocin (50mg/kg) for 5 consecutive days. Eight weeks after streptozotocin injections, DM was determined by measuring blood glucose and body weight. Diabetic mice were treated with two intracavernous administrations of phosphate-buffered saline (20μL) or various doses of HB-EGF (days -3 and 0; 1, 5, and 10μg in 20μL of phosphate-buffered saline). The angiogenesis effect of HB-EGF was confirmed by tube formation and migration assays in mouse cavernous endothelial cells and mouse cavernous pericytes under high-glucose conditions. Erectile function was measured by electrical stimulation of the cavernous nerve, as well as histological examination and Western blot analysis for mechanism assessment. In vitro angiogenesis, cell proliferation, in vivo intracavernous pressure, neurovascular regeneration, cavernous permeability, and survival signaling were the outcomes measured. Expression of HB-EGF was reduced under diabetic conditions. Exogenous HB-EGF induced angiogenesis in mouse cavernous endothelial cells and mouse cavernous pericytes under high-glucose conditions. Erectile function was decreased in the DM group, whereas administration of HB-EGF resulted in a significant improvement of erectile function (91% of the age-matched control group) in association with increased neurovascular content, including cavernous endothelial cells, pericytes, and neuronal cells. Histological and Western blot analyses revealed a significant increase in the permeability of the corpus cavernosum in DM mice, which was attenuated by HB-EGF treatment. The protein expression of phospho-Akt Ser473 and phosphorylated endothelial nitric oxide synthase Ser1177 increased after HB-EGF treatment. The use of HB-EGF may be an effective strategy to treat ED associated with DM or other neurovascular diseases. Similarly to other pro-angiogenic factors, HB-EGF has dual roles in vascular and neuronal development. Our study focused on broadly evaluating the role of HB-EGF in diabetic ED. In view of the properties of HB-EGF as an angiogenic factor, its dose concentration should be strictly controlled to avoid potential side effects. In the diabetic ED mouse model in this study erectile function was improved by HB-EGF, which may provide new treatment strategies for patients with ED who do not respond to phosphodiesterase 5 Inhibitors.

Hyponatraemia-treatment standard 2024.

Hyponatraemia is the most common electrolyte disorder in hospital patients associated with increased morbidity, mortality, hospital stay and financial burden. The speed of a correction with 3% sodium chloride as a 100- to 150-ml intravenous bolus or continuous infusion depends on the severity and persistence of the symptoms and needs frequent biochemical monitoring. The rapid intermittent administration of hypertonic saline is preferred for treatment of symptomatic hyponatraemia. In asymptomatic mild hyponatraemia, an adequate solute intake with an initial fluid restriction (FR) of 500ml/day adjusted according to the serum sodium (sNa) levels is preferred. Almost half of the syndrome of inappropriate antidiuretic hormone (SIADH) patients do not respond to FR as first-line therapy. At present, urea and tolvaptan are considered the most effective second-line therapies in SIADH. However, the evidence for guidance on the choice of second-line therapy of hypotonic hyponatraemia is lacking. Oral urea is considered to be a very effective and safe treatment. Mild and asymptomatic hyponatraemia is treated with adequate solute intake (salt and protein) and initial FR with adjustments based on sNa levels. Specific treatment with vaptans may be considered in either euvolaemic or hypervolaemic patients with high ADH activity. In order to ensure optimal patient outcome, close monitoring and readiness for administration of either hypotonic fluids or desmopressin may be crucial in the decision-making process for specific treatment and eventual overcorrection consequences. According to the guidelines, gradual correction and clinical evaluation is preferable over rapid normalization of sNa towards the laboratory reference ranges.

A Single Injection of ADRCs Does Not Prevent AAA Formation in Rats in a Randomized Blinded Design.

There is a pressing need for alternative medical treatments for abdominal aortic aneurysms (AAAs). Mesenchymal regenerative cells derived from adipose tissue (ADRCs) have shown potential in modulating the inflammation and immune responses that drive AAA progression. We hypothesized that ADRCs could reduce inflammation and preserve vascular integrity, potentially slowing the progression of AAA. In our study, subcutaneous adipose tissue was harvested from male Sprague Dawley rats, from which ADRCs were isolated. AAA was induced in these rats using intraluminal porcine pancreatic elastase, followed by intravenous administration of either ADRCs (106 cells) or saline (0.1 mL). We monitored the progression of AAA through weekly ultrasound, and the rats were sacrificed on day 28 for histological analysis. Our results showed no significant difference in the inner abdominal aortic diameter at day 28 between the control group (172% ± 73%, n = 17) and the ADRC-treated group (181% ± 75%, n = 15). Histological analyses of AAA cross-sections also revealed no significant difference in the infiltration of neutrophils or macrophages between the two groups. Furthermore, the integrity and content of elastin in the tunica media were similar between groups. These findings indicate that a single injection of ADRCs does not inhibit the development of AAA in rats in a randomized blinded study.

Therapeutic effect of epidural dexamethasone palmitate in a rat model of lumbar spinal stenosis

BackgroundDexamethasone palmitate (DEP), a prodrug of dexamethasone (DEX), is a synthetic corticosteroid medication distinguished by the inclusion of a fatty acid component known as palmitate. This study introduces DEP as...

Elevated muscle pain induced by a hypertonic saline injection reduces power output independent of physiological changes during fixed perceived effort cycling.

Pain is a naturally occurring phenomenon that consistently inhibits exercise performance by imposing unconscious, neurophysiological alterations (e.g., corticospinal changes) as well as conscious, psychophysiological pressures (e.g., shared effort demands). Although several studies indicate that pain would elicit lower task outputs for a set intensity of perceived effort, no study has tested this. Therefore, this study investigated the impact of elevated muscle pain through a hypertonic saline injection on the power output, psychophysiological, cerebral oxygenation, and perceptual changes during fixed perceived effort exercise. Ten participants completed three visits (1 familiarization + 2 fixed perceived effort trials). Fixed perceived effort cycling corresponded to 15% above gas exchange threshold (GET) [mean rating of perceived effort (RPE) = 15 "hard"]. Before the 30-min fixed perceived effort exercise, participants received a randomized bilateral hypertonic or isotonic saline injection in the vastus lateralis. Power output, cardiorespiratory, cerebral oxygenation, and perceptual markers (e.g., affective valence) were recorded during exercise. Linear mixed-model regression assessed the condition and time effects and condition × time interactions. Significant condition effects showed that power output was significantly lower during hypertonic conditions [t107 = 208, P = 0.040, β = 4.77 W, 95% confidence interval (95% CI) [0.27 to 9.26 W]]. Meanwhile, all physiological variables (e.g., heart rate, oxygen uptake, minute ventilation) demonstrated no significant condition effects. Condition effects were observed for deoxyhemoglobin changes from baseline (t107 = -3.29, P = 0.001, β = -1.50 ΔμM, 95% CI [-2.40 to -0.61 ΔμM]) and affective valence (t127 = 6.12, P = 0.001, β = 0.93, 95% CI [0.63 to 1.23]). Results infer that pain impacts the self-regulation of fixed perceived effort exercise, as differences in power output mainly occurred when pain ratings were higher after hypertonic versus isotonic saline administration.NEW & NOTEWORTHY This study identifies that elevated muscle pain through a hypertonic saline injection causes significantly lower power output when pain is experienced but does not seem to affect exercise behavior in a residual manner. Results provide some evidence that pain operates on a psychophysiological level to alter the self-regulation of exercise behavior due to differences between conditions in cerebral deoxyhemoglobin and other perceptual parameters.

The Potential Neurological Impact of Intraoperative Hyponatremia Using Histidine-Tryptophan-Ketoglutarate Cardioplegia Infusion in Adult Cardiac Surgery.

Background and Objectives: The relationship between histidine-tryptophan-ketoglutarate (HTK)-induced hyponatremia and brain injury in adult cardiac surgery patients is unclear. This study analyzed postoperative neurological outcomes after intraoperative HTK cardioplegia infusion. Materials and Methods: A prospective cohort study was conducted on 60 adult patients who underwent cardiac surgery with cardiopulmonary bypass. Of these patients, 13 and 47 received HTK infusion and conventional hyperkalemic cardioplegia, respectively. The patients' baseline characteristics, intraoperative data, brain injury markers, Mini-Mental State Examination (MMSE) scores, and quantitative electroencephalography (qEEG) data were collected. Electrolyte changes during cardiopulmonary bypass, the degree of hyponatremia, and any associated brain insults were evaluated. Results: The HTK group presented with acute hyponatremia during cardiopulmonary bypass, which was intraoperatively corrected through ultrafiltration and normal saline administration. Postoperative sodium levels were higher in the HTK group than in the conventional cardioplegia group. The change in neuron-specific enolase levels after cardiopulmonary bypass was significantly higher in the HTK group (p = 0.043). The changes showed no significant differences using case-control matching. qEEG analysis revealed a significant increase in relative delta power in the HTK group on postoperative day (POD) 7 (p = 0.018); however, no significant changes were noted on POD 60. The MMSE scores were not significantly different between the two groups on POD 7 and POD 60. Conclusions: HTK-induced acute hyponatremia and rapid correction with normal saline during adult cardiac surgeries were associated with a potential short-term but not long-term neurological impact. Further studies are required to determine the necessity of correction for HTK-induced hyponatremia.