Parameters In Rat Model Research Articles

MP01-15 THE IN-VIVO EFFICACY OF LOW-INTENSITY SHOCKWAVE THERAPY ON SPERM PARAMETERS IN AN AGED RAT MODEL

You have accessJournal of UrologyCME1 Apr 2023MP01-15 THE IN-VIVO EFFICACY OF LOW-INTENSITY SHOCKWAVE THERAPY ON SPERM PARAMETERS IN AN AGED RAT MODEL Taher Naeem, Gal Saffati, Weitao Song, Thomas Garcia, Mohit Khera, and Manuel Villarreal Taher NaeemTaher Naeem More articles by this author , Gal SaffatiGal Saffati More articles by this author , Weitao SongWeitao Song More articles by this author , Thomas GarciaThomas Garcia More articles by this author , Mohit KheraMohit Khera More articles by this author , and Manuel VillarrealManuel Villarreal More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003212.15AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Low-intensity shockwave therapy (LIST) is a safe, non-invasive therapy and an effective treatment option for erectile dysfunction (ED) and many other etiologies by stimulating angiogenesis in the target tissue. It has been theorized that a similar effect could be observed in infertile patients by stimulating spermatogenesis though very little data exists to determine the in-vivo efficacy thereof. This study seeks to investigate the efficacy of LIST on semen parameters in a rat model with age-induced infertility. METHODS: In this primary experiment, 8 Sprague-Dawley (SD) rats at age 6-months were divided into 2 arms: control (N=4) and treatment (N=4). The treatment group received 600 shocks on the testis (3 site on each side, 100 shocks on each site) per session at 0.10 mJ/mm2 3 times a week for 4 weeks and the control group received placebo shocks. One month after the treatment was complete, the rats were euthanized, and semen samples obtained from the epididymis and analyzed using computer assisted sperm analysis. Statistical analysis was done using non-parametric Wilcoxon testing. RESULTS: Testis weights and testosterone levels were not statistically significantly different between the two groups and semen parameters in the treatment group were not statistically significantly improved from the control group. The only notable improvement was in linearity of the average path of the sperm (p=.0239), though this parameter is not a clinically significant one. Histological analysis of the testes and epididymis is ongoing. CONCLUSIONS: This study suggests that LIST does not have an appreciable effect on semen parameters in a SD rat model. This contradicts a prior study that shows an improvement in semen parameters after LIST using a slightly different energy level of 0.05 mJ/mm2. More work needs to be done to determine if LIST is an effective treatment for male infertility. Source of Funding: McNair Foundation © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e8 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Taher Naeem More articles by this author Gal Saffati More articles by this author Weitao Song More articles by this author Thomas Garcia More articles by this author Mohit Khera More articles by this author Manuel Villarreal More articles by this author Expand All Advertisement PDF downloadLoading ...

Identification of a substrate-like cleavage-resistant thrombin inhibitor from the saliva of the flea Xenopsylla cheopis

The salivary glands of the flea Xenopsylla cheopis, a vector of the plague bacterium, Yersinia pestis, express proteins and peptides thought to target the hemostatic and inflammatory systems of its mammalian hosts. Past transcriptomic analyses of salivary gland tissue revealed the presence of two similar peptides (XC-42 and XC-43) having no extensive similarities to any other deposited sequences. Here we show that these peptides specifically inhibit coagulation of plasma and the amidolytic activity of α-thrombin. XC-43, the smaller of the two peptides, is a fast, tight-binding inhibitor of thrombin with a dissociation constant of less than 10 pM. XC-42 exhibits similar selectivity as well as kinetic and binding properties. The crystal structure of XC-43 in complex with thrombin shows that despite its substrate-like binding mode, XC-43 is not detectably cleaved by thrombin and that it interacts with the thrombin surface from the enzyme catalytic site through the fibrinogen-binding exosite I. The low rate of hydrolysis was verified in solution experiments with XC-43, which show the substrate to be largely intact after 2 h of incubation with thrombin at 37 °C. The low rate of XC-43 cleavage by thrombin may be attributable to specific changes in the catalytic triad observable in the crystal structure of the complex or to extensive interactions in the prime sites that may stabilize the binding of cleavage products. Based on the increased arterial occlusion time, tail bleeding time, and blood coagulation parameters in rat models of thrombosis XC-43 could be valuable as an anticoagulant.

Neuromodulation Effect of Very Low Intensity Transcranial Ultrasound Stimulation on Multiple Nuclei in Rat Brain.

ObjectiveLow-intensity transcranial ultrasound stimulation (TUS) is a non-invasive neuromodulation technique with high spatial resolution and feasible penetration depth. To date, the mechanisms of TUS modulated neural oscillations are not fully understood. This study designed a very low acoustic intensity (AI) TUS system that produces considerably reduced AI Ultrasound pulses (ISPTA < 0.5 W/cm2) when compared to previous methods used to measure regional neural oscillation patterns under different TUS parameters.MethodsWe recorded the local field potential (LFP) of five brain nuclei under TUS with three groups of simulating parameters. Spectrum estimation, time-frequency analysis (TFA), and relative power analysis methods have been applied to investigate neural oscillation patterns under different stimulation parameters.ResultsUnder PRF, 500 Hz and 1 kHz TUS, high-amplitude LFP activity with the auto-rhythmic pattern appeared in selected nuclei when ISPTA exceeded 12 mW/cm2. With TFA, high-frequency energy (slow gamma and high gamma) was significantly increased during the auto-rhythmic patterns. We observed an initial plateau in nuclei response when ISPTA reached 16.4 mW/cm2 for RPF 500 Hz and 20.8 mW/cm2 for RPF 1 kHz. The number of responding nuclei started decreasing while ISPTA continued increasing. Under 1.5 kHz TUS, no auto-rhythmic patterns have been observed, but slow frequency power was increased during TUS. TUS inhibited most of the frequency band and generated obvious slow waves (theta and delta band) when stimulated at RPF = 1.5 kHz, ISPTA = 8.8 mW/cm2.ConclusionThese results demonstrate that very low intensity Transcranial Ultrasound Stimulation (VLTUS) exerts significant neuromodulator effects under specific parameters in rat models and may be a valid tool to study neuronal physiology.

Divergent Effects of Hypertonic Fluid Resuscitation on Renal Pathophysiological and Structural Parameters in Rat Model of Lower Body Ischemia/Reperfusion-Induced Sterile Inflammation.

The pathogenesis of acute kidney injury (AKI) is characterized by the deterioration of tissue perfusion and oxygenation and enhanced inflammation. The purpose of this study was to investigate whether or not the hemodynamic and inflammatory effects of hypertonic saline (HS) protect the kidney by promoting renal microcirculatory oxygenation and possible deleterious effects of HS due to its high sodium content on renal functional and structural injury following ischemia/reperfusion. Mechanically ventilated and anesthetized rats were randomly divided into four groups (n = 6 per group): a sham-operated control group; a group subjected to renal ischemia for 45 min by supra-aortic occlusion followed by 2 h of reperfusion (I/R); and I/R group treated with a continuous i.v. infusion (5 mL/kg/h) of either % 0.9 NaCl (IR+NS) or %10 NaCl (I/R+HS) after releasing the clamp. Systemic and renal hemodynamic, renal cortical (CμPO2), and medullar microcirculatory pO2 (MμPO2) are measured by the oxygen-dependent quenching of the phosphorescence lifetime technique. Renal functional, inflammatory, and tissues damage parameters were also assessed. HS, but not NS, treatment restored I/R-induced reduced mean arterial pressure, CμPO2, renal oxygen deliver (DO2ren), and consumption (VO2ren). HS caused a decrease in tubular sodium reabsorption (TNa) that correlated with an elevation of fractional sodium excretion (EFNa) and urine output. HS had an anti-inflammatory effect by reducing the levels TNF-α, IL-6, and hyaluronic acid in the renal tissue samples as compared with the I/R and I/R+NS groups (P < 0.05). HS treatment was also associated with mild acidosis and an increased renal tubular damage. Despite HS resuscitation improving the systemic hemodynamics, microcirculatory oxygenation, and renal oxygen consumption as well as inflammation, it should be limited or strictly controlled for long-term use because of provoking widespread renal structural damage.

Ovarian failure in diabetic rat model: Nuclear factor-kappaB, oxidative stress, and pentraxin-3

ObjectiveThe aim of the present study was to investigate the effects of diabetes mellitus (DM) on ovarian reserve and injury by considering laboratory and histopathological parameters in rat models. Materials and methodsAn experimental DM model was created in 16 rats. Eight rats with normal blood glucose levels were included in the control group. Diabetic rats were divided randomly into two groups: nontreated and resveratrol-treated groups. Histopathological examination and nuclear factor (NF)-κB immunoexpression level determination were performed. Plasma malondialdehyde, glutathione, pentraxin-3, and anti-Müllerian hormone levels were measured. Relations between the variables were compared by Student t test, analysis of variance, and Mann–Whitney U and χ2 tests. ResultsWe found statistically significantly lower glutathione and anti-Müllerian hormone levels, and higher malondialdehyde and pentraxin-3 levels in nontreated diabetic group when compared with the control and resveratrol-treated diabetic groups. Stromal degeneration, follicle degeneration, stromal fibrosis scores, and NF-κB immunoexpression levels were significantly higher in nontreated diabetic rats. Primordial and primary follicle counts were significantly lower in the nontreated diabetic group when compared with the control and resveratrol-treated groups. There was no statistically significant difference in secondary and tertiary follicles between these groups. ConclusionThese findings provide strong evidence that the ovarian follicle pool in nontreated diabetic rats is affected in the early stages of the follicle development process. We precluded negative effects of DM on ovaries by inhibiting the NF-κB pathway with resveratrol. We thought that the NF-κB pathway plays a role in the pathophysiology of ovarian failure in diabetic rats. Further studies should evaluate this precise mechanism that leads to a decline in the anti-Müllerian hormone levels. In addition, the relationship between this abnormality and reproductive function in diabetic patients should be analyzed further.

A physiologically based pharmacokinetic model for quinoxaline-2-carboxylic acid in rats, extrapolation to pigs.

A multi-compartment physiologically based pharmacokinetic (PBPK) model to describe the disposition of cyadox (CYX) and its metabolite quinoxaline-2-carboxylic acid (QCA) after a single oral administration was developed in rats (200 mg/kg b.w. of CYX). Considering interspecies differences in physiology and physiochemistry, the model efficiency was validated by pharmacokinetic data set in swine. The model included six compartments that were blood, muscle, liver, kidney, adipose, and a combined compartment for the rest of tissues. The model was parameterized using rat plasma and tissue concentration data that were generated from this study. Model simulations were achieved using a commercially available software program (ACSLXL ibero version 3.0.2.1). Results supported the validity of the model with simulated tissue concentrations within the range of the observations. The correlation coefficients of the predicted and experimentally determined values for plasma, liver, kidney, adipose, and muscles in rats were 0.98, 0.98, 0.98, 0.99, and 0.95, respectively. The rat model parameters were then extrapolated to pigs to estimate QCA disposition in tissues and validated by tissue concentration of QCA in swine. The correlation coefficients between the predicted and observed values were over 0.90. This model could provide a foundation for developing more reliable pig models once more data are available.

Assessment of toxic effects of the methanol extract of Citrus macroptera Montr. Fruit via biochemical and hematological evaluation in female Sprague-Dawley rats.

Citrus macroptera Montr. (C. macroptera) is locally known as Satkara. The fruit of this plant is used as appetite stimulant and in the treatment of fever. This study therefore aimed to evaluate the toxic effects of the fruit extract using some biochemical and hematological parameters in rat model. The effects of methanol extract of Citrus macroptera Montr. fruit administered at 250, 500 and 1000 mg/kg body weight were investigated on hematological and biochemical parameters in Sprague-Dawley female rats. Moreover, histopathological study was performed to observe the presence of pathological lesions in primary body organs. The extract presented no significant effect on body weight, percent water content, relative organ weight and hematological parameters in rat. Significant decrease from control group was observed in the levels of triglyceride, total cholesterol, low density lipoprotein and very low density lipoprotein; thus leading to significant decrease of cardiac risk ratio, castelli's risk index-2, atherogenic coefficient and atherogenic index of plasma at all doses. 500 mg/kg dose significantly decreased alkaline phosphatase (P<0.05), 1000 mg/kg dose significantly increased high density lipoprotein cholesterol (P<0.05) and 250 mg/kg dose significantly decreased the level of glycated hemoglobin (P<0.05) from the control group. There were no significant alterations observed with other serum biochemical parameters. Histopathological study confirmed the absence of inflammatory and necrotic features in the primary body organs. Study results indicate that methanolic fruit extract is unlikely to have significant toxicity. Moreover, these findings justified the cardio-protective, moderate hepato-protective and glucose controlling activities of the fruit extract.

Differential Effects of Furnidipines’ Metabolites on Reperfusion-Induced Arrhythmias in Rats In Vivo

We previously established that furnidipine (FUR) and oxy dihydropyridines prevent rats mortality by strong reduction of the lethal arrhythmias in reperfusion. Therefore we decided to study the influence of three main metabolites (M-2, M-3, M-8) of FUR on ischemia-and reperfusion- induced arrhythmias and hemodynamic parameters in rat model to examine their independent activity. The metabolites (M-2, M-3, M-8) were given orally 20 mg/kg (24 and 1 h before ischemia). Mortality was significantly diminished in M-2 and M-3 treated groups with M-3 preventing animal mortality entirely. All three examined substances significantly reduced the duration and incidence of ventricular fibrillation (VF) with M-3, once again, completely preventing VF. Moreover, only M-3 significantly decreased the duration of ventricular tachycardia but had no influence on their incidence. Through the occlusion and reperfusion periods, M-2 and M-3 were markedly less hypotensive than M-8 and did not influence on heart rate. We conclude that two tested metabolites of FUR, M-3 and M-2 exhibited the most pronounced anti-arrhythmic effect being at the same time the most normotensive and therefore caused the most beneficial effects.

A physiologically based pharmacokinetic model for valnemulin in rats and extrapolation to pigs

A flow-limited, physiologically based pharmacokinetic (PBPK) model for predicting the plasma and tissue concentrations of valnemulin after a single oral administration to rats was developed, and then the data were extrapolated to pigs so as to predict withdrawal interval in edible tissues. Blood/tissue pharmacokinetic data and blood/tissue partition coefficients for valnemulin in rats and pigs were collected experimentally. Absorption, distribution and elimination of the drug were characterized by a set of mass-balance equations. Model simulations were achieved using a commercially available software program. The rat PBPK model better predicted plasma and tissue concentrations. The correlation coefficients of the predicted and experimentally determined values for plasma, liver, kidney, lung and muscle were 0.96, 0.94, 0.96, 0.91 and 0.91, respectively. The rat model parameters were extrapolated to pigs to estimate valnemulin residue withdrawal interval in edible tissues. Correlation (R(2) ) between predicted and observed liver, kidney and muscle were 0.95, 0.97 and 0.99, respectively. Based on liver tissue residue profiles, the pig model estimated a withdrawal interval of 10 h under a multiple oral dosing schedule (5.0 mg/kg, twice daily for 7.5 days). PBPK models, such as this one, provide evidence of the usefulness in interspecies PK data extrapolation over a range of dosing scenarios and can be used to predict withdrawal interval in pigs.

Cardiovascular parameters in rat model of chronic renal failure induced by subtotal nephrectomy

Chronic renal failure (CRF) is associated with high incidence of cardiovascular complications. To clarify pathogenesis of CRF numerous animal models have been developed. The aim of our work was to describe methodology of subtotal surgical renal ablation in rat and to characterize some biochemical and cardiovascular parameters of this animal model. Male rats underwent 5/6 surgical nephrectomy or sham operations in two steps. The following parameters were measured on day 10 and in week 10 after the surgery: plasma concentrations of creatinine and urea, blood pressure, resting heart rate, chronotropic response to atropine and metipranol, heart ventricles weight, contraction parameters and action potential duration in the left ventricle. Increased serum concentrations of creatinine and urea, decreased creatinine clearance, polyuria and alteration of the remnant kidney tissue were found in CRF rats. Changes in cardiovascular parameters identified after subtotal nephrectomy resembled alterations of cardiovascular system in uremic patients and included hypertension, elevated resting heart rate, diminished parasympathetic cardiac tone, hypertrophy of the left ventricle associated with weakened force of contraction, prolonged contraction and relaxation and shortening of action potential duration. These data suggest that the present model can be a useful tool in the study of CRF and its cardiovascular complications.

Comparative effects of dietary administered transgenic and conventional papaya on selected intestinal parameters in rat models

Transformation of agricultural crops with novel genes has significantly advanced disease-resistance breeding, including virus resistance through the expression of virus sequences. In this study, the effects of long-term, repeated exposure to transgenic papayas carrying the coat protein gene of Papaya ringspot virus and conventional non-transgenic papaya on the histology and selected biochemical parameters of the intestinal tract were compared. For 3 months, male and female Wistar rats received diets containing transgenic or non-transgenic papaya at twice the equivalent of the average daily consumption of fresh papayas. Gross and macroscopic appearance of intestinal tissues, as well as stomach tissues, was comparable (P < 0.05) as were total intestinal bacterial counts and activities of beta-glucuronidase. Activities of disaccharidases were not affected, neither were those of amylase (P < 0.05). Although significant differences were noted in the activity of Ca(2+) and Na(+)/K(+) ATPase brush border enzymes, no morphological alteration in the integrity of the intestinal mucosa was found. Overall, negligible effects on feed intake, body weight, and fecal output were observed (P < 0.05). Taken together, long-term exposure to diets formulated with transgenic papaya did not result in biologically important unintended effects.

Gemals, a new drug candidate, extends lifespan and improves electromyographic parameters in a rat model of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal disease involving selective and progressive degeneration and death of motor neurons. ALS is a multifactorial disease in which oxidative stress, glutamate excitotoxicity, intracellular aggregates, neurofilamentous disorganization, zinc excitotoxicity, mitochondrial damage, neuroinflammation, abnormalities in growth factors and apoptosis play a role. Any therapeutic approach to delay or stop the evolution of ALS should therefore ideally target these multiple pathways leading to motor neuron death. We have developed a combination therapy (Gemals) composed of functional polypeptides (fatty acids, free radical scavengers and amino acids linked to poly-L-lysine), chosen according to their known potentiality for regeneration or protection of neuronal components such as myelin, axon transport and mitochondria. We found that Gemals significantly extended lifespan and improved electromyographic parameters in a SOD1(G93A) rat model. The use of two drug concentrations indicated a possible dose dependence. These initial findings open the way to further investigation necessary to validate this new drug as a candidate for ALS treatment.

Effect of osmolarity on canine renal vascular resistance.

ARTICLESEffect of osmolarity on canine renal vascular resistanceS Gazitua, JB Scott, CC Chou, and FJ HaddyS Gazitua, JB Scott, CC Chou, and FJ HaddyPublished Online:01 Oct 1969https://doi.org/10.1152/ajplegacy.1969.217.4.1216MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByDivergent Effects of Hypertonic Fluid Resuscitation on Renal Pathophysiological and Structural Parameters in Rat Model of Lower Body Ischemia/Reperfusion-Induced Sterile InflammationShock, Vol. 50, No. 6Is Contrast Medium Osmolality a Causal Factor for Contrast-Induced Nephropathy?BioMed Research International, Vol. 2014Hypertonic saline solution for prevention of renal dysfunction in patients with decompensated heart failureInternational Journal of Cardiology, Vol. 167, No. 1Impact of Hypertonic and Hyperoncotic Saline Solutions on 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hypertonic or colloid infusions immediately after mitral valve repairCritical Care Medicine, Vol. 27, No. 10Fluid and Electrolyte Disorders in the Surgical PatientSmall-volume Resuscitation beim hypovolämischen Schock7 November 2016 | Der Anaesthesist, Vol. 46, No. 4Effect of 7.2% Hypertonic Saline/6% Hetastarch on Left Ventricular Contractility in Anesthetized HumansAnesthesiology, Vol. 82, No. 6Fluid and Electrolyte Disorders in the Surgical PatientHaemodynamic effects of small volume hypertonic saline in experimentally induced haemorrhagic shockEquine Veterinary Journal, Vol. 22, No. 4Chlorure de sodium hypertonique et choc hémorragiqueAnnales Françaises d'Anesthésie et de Réanimation, Vol. 9, No. 6Treatment of uncontrolled hemorrhagic shock by hypertonic saline and external counterpressureAnnals of Emergency Medicine, Vol. 18, No. 10Small-volume resuscitationBaillière's Clinical Anaesthesiology, Vol. 2, No. 3Analysis of the cardiovascular effects of arginine vasopressin in conscious dogs.Hypertension, Vol. 9, No. 4A comparison of several hypertonic solutions for resuscitation of bled sheepJournal of Surgical Research, Vol. 39, No. 6The peritoneal microcirculationThe effect of hyponatremia on the regulation of intracellular volume and solute composition.Circulation Research, Vol. 54, No. 5Contrast Media in the Cardiovascular SystemInduced hyperosmolality effects on extracellular fluid volume, lymph flow and osmolar equilibrium: studies in the ratActa Physiologica Scandinavica, Vol. 116, No. 3Feedback-mediated reduction of glomerular filtration rate during infusion of hypertonic salineKidney International, Vol. 20, No. 4The Peritoneal MicrocirculationEffect of Local Metabolic Factors on Vascular Smooth Muscle1 January 2011In situ hypothermic renal perfusion Evaluation of three intracellular solutionsUrology, Vol. 15, No. 5The mechanism of neuronal noradrenaline and dopamine β-hydroxylase release by a sodium-deficient solution substituted with ureaNeuroscience, Vol. 5, No. 2Microvascular and clinical effects of altered peritoneal dialysis solutionsKidney International, Vol. 15, No. 6Management of 136 consecutive supratentorial berry aneurysmsJournal of Neurosurgery, Vol. 49, No. 6Hyper/Hypo-Osmotic Peritoneal Dialysis7 July 2009 | Journal of Dialysis, Vol. 2, No. 5-6Fetal pathology and mechanism of fetal death in saline-induced abortion: A study of 143 gestations and critical review of the literatureAmerican Journal of Obstetrics and Gynecology, Vol. 120, No. 3Ex vivo renal surgeryThe American Journal of Surgery, Vol. 128, No. 3Experiments in Renal Preservation: 48 and 72-hour Canine Kidney Preservation by Initial Perfusion and Hypothermic StorageJournal of Urology, Vol. 111, No. 4Mechanism of the acute pressor action of hypokalemia, hypomagnesemia, and hypo-osmolalityAmerican Heart Journal, Vol. 85, No. 5CANINE KIDNEY PRESERVATION USING A NEW PERFUSATEThe Lancet, Vol. 301, No. 7811The Nature of Renal Perfusion in Normal, Oliguric and Anuric States29 October 2018 | Urologia Journal, Vol. 39, No. 6Influence of Plasma Hypertonicity on Blood Viscosity Studied in Vitro and in an Isolated Vascular BedActa Physiologica Scandinavica, Vol. 84, No. 4Effects of renal artery infusion of various hypertonic solutions on the renal blood flow and renal handling of PAH in the dogPfl�gers Archiv European Journal of Physiology, Vol. 334, No. 1 More from this issue > Volume 217Issue 4October 1969Pages 1216-1223 Copyright & PermissionsCopyright © 1969 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1969.217.4.1216PubMed5824323History Published online 1 October 1969 Published in print 1 October 1969 Metrics