The Effect of Gelatin Molecular Weight on Tendon Lubrication Utilizing an Extrasynovialized Turkey Flexor Tendon Model

ABSTRACT Introduction Flexor tendon injuries are common hand injuries among the military population often resulting in functional impairment. Flexor tendon gliding friction has been linked to adhesion formation, especially with the use of extrasynovial grafts. Carbodiimide-derivatized hyaluronic acid with gelatin (cd-HA-gelatin) can reduce gliding friction of the tendon graft; however, the effects of gelatin molecular weight (MW) have not been studied. The turkey model has been shown to better match humans, but extrasynovial tendons are unavailable. The purpose of this study was to (1) manually roughen turkey flexor digitorum profundus (FDP) tendons to simulate extrasynovial tendons and (2) investigate the effects of gelatin MW on tendon friction. Materials and Methods The third digit of (n = 48) turkeys were dissected with the proximal pulley, and FDP tendon and the flexor superficialis tendon were preserved. Digits were randomly assigned into four groups: one saline control and three cd-HA-gelatin-treated groups of varying gelatin MW. Flexor digitorum profundus tendon friction was measured at its original condition, serving as a baseline. Tendons were roughened using a custom rig, and tendon friction was measured again. All four groups received treatment and gliding friction was measured every 100 cycles to a total of 1,000 cycles. Results Tendon friction significantly increased (P < 0.05) after roughening. Friction in the saline control group increased steadily over repeated cycles, whereas friction of all gelatin-treated tendons decreased significantly compared with the saline control group (P < 0.05), maintaining low friction to 1,000 cycles representing human tendons. There was no significant difference found between gelatin-treated groups. Conclusions We have developed a method to roughen synovial FDP tendons to create extrasynovial-like tendons for lubrication material evaluations. Cd-HA-gelatin effectively reduces tendon friction in this model. Our data suggest medium or low MW gelatin may provide a better reduction in friction compared with high MW gelatin.

Interspecific Mating Effects on Locomotor Activity Rhythms and Refractoriness of Aedes albopictus (Diptera: Culicidae) Females

This study tests the hypotheses that the locomotor activity of Ae. albopictus females is not significantly altered by the presence of accessory gland (AG) extracts from conspecific and heterospecific males, and that Ae. albopictus females remain receptive to mating with conspecific males even after receiving AG of Ae. aegypti males. Virgin Ae. albopictus females were injected with saline (control group), AG extracts of Ae. aegypti males (aegMAG) or AG extracts of Ae. albopictus males (albMAG). Locomotor activity was evaluated under 12 h of light and 12 h of darkness at 25 °C. All live Ae. albopictus females were subsequently exposed to conspecific males for 48 h, and their spermathecae were dissected for the presence of sperm. Females injected with aegMAG and albMAG showed significant decreases in total, diurnal and diurnal without lights-on Period activities. Females injected with aegMAG showed significant decreases in nocturnal and nocturnal without lights-off period activities. Females injected with albMAG showed significant decreases in lights-off activity. A total of 83% of Ae. albopictus females injected with aegMAG and 10% of females injected with albMAG were inseminated by conspecific males. These results, coupled with our previous paper on MAG and interspecific mating effects on female Ae. aegypti, demonstrate contrasting outcomes on locomotor activities and loss of sexual receptivity, both conspecific and heterospecific MAGs capable of sterilizing virgin Ae. aegypti, but only conspecific MAGs sterilizing Ae. albopictus, whereas locomotor activities were depressed in females of both species after heterospecific and conspecific injections or treatments.

Effect of Ultramicro Superparamagnetic Iron Oxide Nanoparticles on Cerebral Infarction in Mice

To investigate the effect of Feraheme (ferumoxytol) intravenous injection on cerebral infarction volume and inflammatory response in mice with permanent middle cerebral artery occlusion. We randomly divided 30 CS7BL6J mice into sham operated group, normal saline control group, and Feraheme group with 10 mice in each group. The model of permanent occlusion of right middle cerebral artery was made via the modified suture method in the normal saline control group and the Feraheme group. After 24 h of establishment the model, the tail vein was injected with 18 mg/kg Feraheme in the sham operation group and Feraheme group, and the normal saline control group was injected with an equal volume of normal saline. Neurobehavioral scores were obtained 24 h (before injection of Feraheme or normal saline) and 48 h (before MRI) after the model was established. The volume of cerebral infarction was calculated according to T2 weighted imaging. Orbital blood was collected after nodal scanning to detect serum TNF-α, IL-1β, and IL-6 levels. Then, the brain tissues of mice were killed for HE staining and IBAL immunohistochemical staining. No significant differences in cerebral infarction volume and neurological function were observed between the normal saline control group and Feraheme group. The levels of TNF-α, IL-1β and IL-6 in the normal saline control group and Feraheme group were significantly higher than those in the sham operation group (P < 0.05), but there were no significant differences between the normal saline control group and Feraheme group. We showed that intravenous injection of 18 mg/kg Feraheme 24 h after cerebral ischemia does not affect the infarct volume and inflammatory response, suggesting that the dose of Feraheme can be used for molecular imaging studies of inflammatory response after cerebral ischemia.

Effects Of Orally Administered Recombinant Lactobacillus Casei Expressing HN Protein On Early Growth Performance, Intestinal Health And Protection Against NDV Challenge In Chickens

Backgroud: Newcastle disease virus (NDV) is considered one of the most important diseases among chickens. In this study, we generated recombinant surface-displayed Lactobacillus casei (L.casei) expressing the hemagglutinin-neuraminidase (HN) of NDV and a live vector pPG alone (named Lc-pPG-HN and Lc-pPG), and evaluated their effects on early growth development, intestinal health and protection against NDV challenge in chickens. 270 chickens were randomly divided into three groups: Lc-pPG-HN, Lc-pPG and physiological saline (control) group, and chickens from each group were respectively immunized with Lc-pPG-HN, Lc-pPG and physiological saline on 1 and 10 days. Results: Recombinant L.casei expressing the HN protein of NDV (Lc-pPG-HN) was successfully constructed. Orally immunized with Lc-pPG-HN could significantly increase body weight (BW) and immune organs index. Moreover, Lc-pPG-HN improved secretory immunoglobulin A (SIgA) in jejunum, the relative abundance of flora in cecum, histomorphological development of small intestine. In addition, the similar enhancement effects were also observed with hemaggluti-nation inhibition (HI) antibody titer and the expression of cytokines in the serum. The oral administration of Lc-pPG-HN also provided effective protection and alleviated the symptoms of NDV challenge.Conclusions: Thus, a recombinant L.casei vaccine expressing HN may be a potential therapeutic candidate against NDV and improve chickens growth and development.

Doxorubicin triggers splenic contraction and irreversible dysregulation of COX and LOX that alters the inflammation-resolution program in the myocardium

Doxorubicin (DOX) is a widely used drug for cancer treatment as a chemotherapeutic agent. However, the cellular and integrative mechanism of DOX-induced immunometabolism is unclear. Two-month-old male C57BL/6J mice were divided into high- and low-dose DOX-treated groups with a maintained saline control group. The first group was injected with a high dose of DOX (H-DOX; 15 mg·kg−1·wk−1), and the second group was injected with 7.5 mg·kg−1·wk−1 as a latent low dose of DOX (LL-DOX). H-DOX treatment led to complete mortality in 2 wk and 70% survival in the LL-DOX group compared with the saline control group. Therefore, an additional group of mice was injected with an acute high dose of DOX (AH-DOX) and euthanized at 24 h to compare with LL-DOX and saline control groups. The LL-DOX and AH-DOX groups showed obvious apoptosis and dysfunctional and structural changes in cardiac tissue. Splenic contraction was evident in AH-DOX- and LL-DOX-treated mice, indicating the systems-wide impact of DOX on integrative organs of the spleen, which is essential for cardiac homeostasis and repair. DOX dysregulated splenic-enriched immune-sensitive lipoxygenase and cyclooxygenase in the spleen and left ventricle compared with the saline control group. As a result, lipoxygenase-dependent D- and E-series resolvin precursors, such as 16HDoHE, 4HDoHE, and 12-HEPE, as well as cyclooxygenase-mediated PG species (PGD2, PGE2, and 6-keto-PG2α) were decreased in the left ventricle, suggestive of defective immunometabolism. Both AH-DOX and LL-DOX induced splenic contraction and expansion of red pulp with decreased CD169+ metallophilic macrophages. AH-DOX intoxicated macrophages in the spleen by depleting CD169+ cells in the acute setting and sustained the splenic macrophage loss in the chronic phase in the LL-DOX group. Thus, DOX triggers a vicious cycle of splenocardiac cachexia to facilitate defective immunometabolism and irreversible macrophage toxicity and thereby impaired the inflammation-resolution program. NEW & NOTEWORTHY Doxorubicin (DOX) triggered splenic mass loss and decreased CD169 with germinal center contraction in acute and chronic exposure. Cardiac toxicity of DOX is marked with dysregulation of immunometabolism and thereby impaired resolution of inflammation. DOX suppressed physiological levels of cytokines and chemokines with signs of splenocardiac cachexia.

Effects of intravenous infusion of E.coli lipopolysaccharide in early pregnant cows

The objective was to characterize effects of Escherichia coli LPS (given iv) on corpus luteum (CL) and embryonic viability in early pregnant cattle. Eight non-lactating German Holstein cows were given 0.5 µg/kg LPS on 35 ± 3 d (mean ± SEM) of pregnancy, whereas seven heifers, 41 ± 6 d pregnant, were given 10 ml saline (Control group). Transrectal B-mode examinations of the CL were done at -1, 3, 6, 12, 24, 48, 72, and 96 h relative to treatment. Blood samples were collected at -1, 0.5, 1, 2, 3, 4, 6, 9, 12, 24, 48, 72, and 96 h. At 12 and 48 h, the CL was biopsied. None of the cows still in the experiment 10 d after LPS (n=7) had embryonic loss. In LPS-treated cows, luteal area decreased (from 4.1 to 3.1 cm2; P≤0.05) within 6 h and until 48 h. Luteal blood flow decreased by 39% (P≤0.05) within the first 6 h after LPS, but returned to pre-treatment values by 48 h. Plasma P4 decreased by 62% (P≤0.05), reached a nadir (2.7±0.6 ng/mL) at 12 h after LPS and was not restored to pre-treatment (P≤0.05). In luteal tissue, mRNAs for StAR and for FGF1 were lower (P≤0.05) in LPS- than in saline-treated cattle at 12 h, with no difference between groups at 48 h. Levels of mRNAs for Casp3 and FGF2 were not different between groups (P>0.05) at 12 or 48 h after treatment. In conclusion, LPS transiently suppressed CL function, but did not induce embryonic mortality.

Local Silver Nanoparticles Administration Promotes Inflammation and Hyperalgesia in Rats

Silver has no known function in the organism. However, nanosilver has the highest degree of commercialization of all nanomaterials used in healthcare. The aim of this study was to assess the potential deleterious effect of local nanosilver administration in an animal model. Wistar rats received a subcutaneous injection (hind paw) of either 500ppm nanosilver (group S1), 20ppm nanosilver (group S2) or saline (control group). Animals were tested by means of plantar test, analgesy-meter and plethysmometer. 24 h after the administration, l-carrageenan was injected (same site), which lead to localized inflammation. The above-mentioned assessments were performed repeatedly until 24 h after l-carrageenan administration. 24 h after colloidal silver administration, both S1 and S2 groups had a significantly higher sensibility to mechanical stimuli. 48 h after colloidal silver administration, the S1 group had a significantly higher sensibility to thermal stimuli. Paw edema was more pronounced in the treatment groups in the first 30 h after the nanosilver injection. Local subcutaneous nanosilver administration leads to an increased inflammatory response and to hyperalgesia. Considering the constant increase in nanosilver�s biomedical use, the current paper sends a clear warning for the need of urgent more in-depth research on the matter.

Influences of Anlotinib on Cytochrome P450 Enzymes in Rats Using a Cocktail Method

The present study aimed to investigate the effect of anlotinib (AL3818) on pharmacokinetics of cytochrome P450 (CYP) enzymes (CYP1A2, CYP2C6, CYP2D1, CYP2D2, and CYP3A1/2) by using five cocktail probe drugs in vivo. After pretreatment for 7 days with anlotinib (treatment group) or saline (control group) by oral administration, probe drugs phenacetin, tolbutamide, omeprazole, metoprolol, and midazolam were administered to rats by oral administration. Blood samples were obtained at a series of time-points and the concentrations of five probe drugs in plasma were determined by a UHPLC-MS/MS method. The results showed that treatment with anlotinib had no significant effect on rat CYP1A2, CYP2D2, and CYP2C6. However, anlotinib had a significant inductive effect on CYP2D1 and CYP3A1/2. Therefore, caution is needed during the concomitant use of anlotinib with other drugs metabolized by CYP2D1 and CYP3A1/2 because of potential drug-anlotinib interactions.

Single dose intratympanic mesna application inhibits propylene glycol induced cholesteatoma formation

Objective:Mesna (i.e. sodium 2-mercaptoethanesulfonate; C2H5NaO3S2) has been used in otological surgery such as cholesteatoma dissection and tympanic membrane lateralisation in atelectatic ears. However, this study aimed to investigate its effect on cholesteatoma formation.Methods:A total of 20 Wistar rats were divided into two groups of 10 animals. The right and left ears of control animals were treated with saline (saline control group; n = 10 ears) and propylene glycol plus saline (propylene glycol control group; n = 10 ears), respectively. In the mesna group, both ears were treated with propylene glycol plus mesna (n = 20 ears). On days 1, 8 and 15, the saline control group had intratympanic injections of 0.2 ml saline and the propylene glycol control and mesna groups had intratympanic injections of 0.2 ml 100 per cent propylene glycol. On day 22, the propylene glycol control group had a single intratympanic injection of 0.2 ml saline and the mesna group had a single intratympanic injection of 10 per cent mesna. Animals were killed 12 weeks after the last injection and the temporal bones were sent for histopathological evaluation.Results:The cholesteatoma formation rate was 88 per cent in the propylene glycol control group, but was significantly lower in the mesna group (p = 0.01). There were no significant differences in granulation tissue formation (p = 0.498), cyst formation in the bulla (p = 0.381), fibrosis (p = 0.072) and epithelial hyperplasia (p = 0.081) among experimental groups.Conclusion:Intratympanic propylene glycol administration is an effective method of promoting experimental cholesteatoma formation. Administration of a single dose of intratympanic mesna inhibited cholesteatoma formation in an animal model.

Morphine Decreases Social Interaction of Adult Male Rats, While THC Does Not Affect It

The aim of the present study was to compare effect of three low doses of morphine (MOR) and delta9-tetrahydrocannabinol (THC) on social behavior tested in Social interaction test (SIT). 45 min prior to testing adult male rats received one of the drugs or solvents: MOR (1; 2.5; 5 mg/kg); saline as a solvent for MOR; THC (0.5; 1; 2 mg/kg); ethanol as a solvent for THC. Occurrence and time spent in specific patterns of social interactions (SI) and non-social activities (locomotion and rearing) was video-recorded for 5 min and then analyzed. MOR in doses of 1 and 2.5 mg/kg displayed decreased SI in total. Detailed analysis of specific patterns of SI revealed decrease in mutual sniffing and allo-grooming after all doses of MOR. The highest dose (5 mg/kg) of MOR decreased following and increased genital investigation. Rearing activity was increased by lower doses of MOR (1 and 2.5 mg/kg). THC, in each of the tested doses, did not induce any specific changes when compared to matching control group (ethanol). However, an additional statistical analysis showed differences between all THC groups and their ethanol control group when compared to saline controls. There was lower SI in total, lower mutual sniffing and allo-grooming, but higher rearing in THC and ethanol groups than in saline control group. Thus, changes seen in THC and ethanol groups are seemed to be attributed mainly to the effect of the ethanol. Based on the present results we can assume that opioids affect SI more than cannabinoid.