scholarly journals Resolution and Prevention of Feline Immunodeficiency Virus-Induced Neurological Deficits by Treatment with the Protease Inhibitor TL-3

2004 ◽  
Vol 78 (9) ◽  
pp. 4525-4532 ◽  
Author(s):  
Salvador Huitron-Resendiz ◽  
Sohela de Rozières ◽  
Manuel Sanchez-Alavez ◽  
Bernd Bühler ◽  
Ying-Chuan Lin ◽  
...  

ABSTRACT In vivo tests were performed to assess the influence of the protease inhibitor TL-3 on feline immunodeficiency virus (FIV)-induced central nervous system (CNS) deficits. Twenty cats were divided into four groups of five animals each. Group 1 received no treatment, group 2 received TL-3 only, group 3 received FIV strain PPR (FIV-PPR) only, and group 4 received FIV-PPR and TL-3. Animals were monitored for immunological and virological status, along with measurements of brain stem auditory evoked potential (BAEP) changes. Groups 1 and 2 remained FIV negative, and groups 3 and 4 became virus positive and seroconverted by 3 to 5 weeks postinoculation. No adverse effects were noted with TL-3 only. The average peak viral load for the virus-only group 3 animals was 1.32 × 106 RNA copies/ml, compared to 6.9 × 104 copies/ml for TL-3-treated group 4 cats. Group 3 (virus-only) cats exhibited marked progressive delays in BAEPs starting at 2 weeks post virus exposure, which is typical of infection with FIV-PPR. In contrast, TL-3-treated cats of group 4 exhibited BAEPs similar to those of control and drug-only cats. At 97 days postinfection, treatments were switched; i.e., group 4 animals were taken off TL-3 and group 3 animals were treated with TL-3. BAEPs in group 3 animals returned to control levels, while BAEPs in group 4 animals remained at control levels. After 70 days on TL-3, group 3 was removed from the drug treatment regimen. Delays in BAEPs immediately increased to levels observed prior to TL-3 treatment. The findings show that early TL-3 treatment can effectively eliminate FIV-induced changes in the CNS. Furthermore, TL-3 can counteract FIV effects on the CNS of infected cats, although continued treatment is required to maintain unimpaired CNS function.

VASA ◽  
2020 ◽  
Vol 49 (4) ◽  
pp. 281-284
Author(s):  
Atıf Yolgosteren ◽  
Gencehan Kumtepe ◽  
Melda Payaslioglu ◽  
Cuneyt Ozakin

Summary. Background: Prosthetic vascular graft infection (PVGI) is a complication with high mortality. Cyanoacrylate (CA) is an adhesive which has been used in a number of surgical procedures. In this in-vivo study, we aimed to evaluate the relationship between PVGI and CA. Materials and methods: Thirty-two rats were equally divided into four groups. Pouch was formed on back of rats until deep fascia. In group 1, vascular graft with polyethyleneterephthalate (PET) was placed into pouch. In group 2, MRSA strain with a density of 1 ml 0.5 MacFarland was injected into pouch. In group 3, 1 cm 2 vascular graft with PET piece was placed into pouch and MRSA strain with a density of 1 ml 0.5 MacFarland was injected. In group 4, 1 cm 2 vascular graft with PET piece impregnated with N-butyl cyanoacrylate-based adhesive was placed and MRSA strain with a density of 1 ml 0.5 MacFarland was injected. All rats were scarified in 96th hour, culture samples were taken where intervention was performed and were evaluated microbiologically. Bacteria reproducing in each group were numerically evaluated based on colony-forming unit (CFU/ml) and compared by taking their average. Results: MRSA reproduction of 0 CFU/ml in group 1, of 1410 CFU/ml in group 2, of 180 200 CFU/ml in group 3 and of 625 300 CFU/ml in group 4 was present. A statistically significant difference was present between group 1 and group 4 (p < 0.01), between group 2 and group 4 (p < 0.01), between group 3 and group 4 (p < 0.05). In terms of reproduction, no statistically significant difference was found in group 1, group 2, group 3 in themselves. Conclusions: We observed that the rate of infection increased in the cyanoacyrylate group where cyanoacrylate was used. We think that surgeon should be more careful in using CA in vascular surgery.


2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Yuqing Zhou ◽  
Qian Dong ◽  
Rong Zhang ◽  
Shunfeng Zhou ◽  
Linqiang Li ◽  
...  

Aims.To investigate cerebral hemodynamics in cirrhotic patients with HE and to observe effects of treatment in cerebral hemodynamics and correlations among ammonia, cerebral hemodynamics, and cognitive function.Methods. There were four groups: healthy controls (group 1), cirrhosis without HE (group 2), cirrhosis with MHE (group 3), and cirrhosis with OHE (group 4). Ammonia and cerebral hemodynamics (by TCD) were assessed. Patients in group 3 were subsequently randomized to two subgroups: the control (group A) and the treated (group B, treated with lactulose for two months), and they were retested for ammonia and TCD after treatment. Results. Ammonia,Vm,Vd, PI, and RI were statistically different before treatment, and ammonia, PI, and RI levels paralleled the severity of HE (P<0.05). In group B,Vdincreased and ammonia, PI, and RI declined following treatment (P<0.05), while there were no differences in group A (P>0.05). Correlations were found between ammonia andVd, PI, RI, NCT-A, and DST and also found betweenVd, PI, RI, and NCT-A and DST (P<0.05).Conclusions. This study revealed that cerebral hemodynamics were related to the severity of HE and cerebral autoregulation was impaired. There were tight correlations among ammonia, cerebral hemodynamics, and cognitive function, and, following treatment, cerebral hemodynamics improved.


2020 ◽  
Vol 30 (11) ◽  
pp. 5863-5873
Author(s):  
Kaicheng Li ◽  
Shuyue Wang ◽  
Xiao Luo ◽  
Qingze Zeng ◽  
Yerfan Jiaerken ◽  
...  

Abstract During the progression of Alzheimer’s disease (AD), neuropathology may propagate transneuronally, cause disruption in memory circuit, and lead to memory impairment. However, there is a lack of in vivo evidence regarding this process. Thus, we aim to simulate and observe the progression of neuropathology in AD continuum. We included cognitively normal (CN), mild cognitive impairments (MCI), and AD subjects, and further classified them using the A/T/N scheme (Group 0: CN, A − T−; Group 1: CN, A + T−; Group 2: CN, A + T+; Group 3: MCI, A + T+; Group 4: AD, A + T+). We investigated alterations of three core memory circuit structures: hippocampus (HP) subfields volume, cingulum-angular bundles (CAB) fiber integrity, and precuneus cortex volume. HP subfields volume showed the trend of initially increased and then decreased (starting from Group 2), while precuneus volume decreased in Groups 3 and 4. The CAB integrity degenerated in Groups 3 and 4 and aggravated with higher disease stages. Further, memory circuit impairments were correlated with neuropathology biomarkers and memory performance. Conclusively, our results demonstrated a pattern of memory circuit impairments along with AD progression: starting from the HP, then propagating to the downstream projection fiber tract and cortex. These findings support the tau propagation theory to some extent.


2006 ◽  
Vol 14 (2) ◽  
pp. 105-110 ◽  
Author(s):  
Mário Tanomaru Filho ◽  
José Carlos Yamashita ◽  
Mario Roberto Leonardo ◽  
Léa Assed Bezerra da Silva ◽  
Juliane Maria Guerreiro Tanomaru ◽  
...  

The aim of this study was to evaluate the antimicrobial effect of biomechanical preparation using different irrigating solutions. Seventy-eight root canals from premolars of four dogs were used. After experimental induction of periapical lesions, the root canals were prepared using the following solutions for irrigation: Group 1) 2.5% sodium hypochlorite (NaOCl); Group 2) 2% chlorhexidine (CHX); Group 3) saline solution and Group 4) control group with no biomechanical preparation. The microbiological evaluation of the root canals was performed by counting the colony forming units (CFUs) using different culture mediums. Two absorbent paper cones were used in each root canal in order to collect the microbiological samples before, and thirty days after the biomechanical preparation. The culture plates were incubated in aerobic, anaerobic and microaerophilic environment. Statistical evaluation was carried out using analysis of variance, Tukey and Student tests. The results demonstrated that there was reduction in the number of microorganisms in the NaOCl and CHX groups (p<0.05). There was greater effectiveness in the chlorhexidine group. The group that used saline solution and the control group presented an increased number of microorganisms. It can be concluded that the use of antimicrobial irrigating solutions during biomechanical preparation promotes the reduction of endodontic microbiota. However, a considerable number of microorganisms were still observed.


2015 ◽  
Vol 2015 ◽  
pp. 1-7
Author(s):  
Khaled Shahrour ◽  
Rick Keck ◽  
Jerzy Jankun

PAI-1 prevents lysis of blood clot by inhibiting the urokinase and tPA induced conversion of plasminogen to plasmin. VLHL PAI-1 protein mutant was created to extend half-life over 700 hours. The objective of this paper was to test VLHL PAI-1 effects on bleeding during partial nephrectomy in mice. All animals had a left partial nephrectomy after intravenous infusion of saline or tPA. The animals were divided into four groups. Group 1 was infused with saline and kidney was exposed to saline too; Group 2 was infused with saline and kidney was exposed to PAI-1. Group 3 was infused with tPA and kidney was exposed to saline, while Group 4 was infused with tPA and kidney was exposed to PAI-1. Preweighed gauze containing PAI-1 or saline was then applied to the kidney for 30 minutes. The gauze was afterward weighed and blood loss was measured by subtracting the preweight of gauze from the final weight. We have observed a statistically significant (P≤0.05) reduction of bleeding in PAI-1-treated group in comparison to saline and tPA-treated groups. Based on these results we propose that VLHL PAI-1 can be used therapeutically in limiting the flow of blood from renal wounds.


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Bernhard Kraemer ◽  
Christian Wallwiener ◽  
Taufiek K. Rajab ◽  
Christoph Brochhausen ◽  
Markus Wallwiener ◽  
...  

Animal models for adhesion induction are heterogeneous and often poorly described. We compare and discuss different models to induce peritoneal adhesions in a randomized, experimental in vivo animal study with 72 female Wistar rats. Six different standardized techniques for peritoneal trauma were used: brushing of peritoneal sidewall and uterine horns (group 1), brushing of parietal peritoneum only (group 2), sharp excision of parietal peritoneum closed with interrupted sutures (group 3), ischemic buttons by grasping the parietal peritoneum and ligating the base with Vicryl suture (group 4), bipolar electrocoagulation of the peritoneum (group 5), and traumatisation by electrocoagulation followed by closure of the resulting peritoneal defect using Vicryl sutures (group 6). Upon second look, there were significant differences in the adhesion incidence between the groups (P<0.01). Analysis of the fraction of adhesions showed that groups 2 (0%) and 5 (4%) were significantly less than the other groups (P<0.01). Furthermore, group 6 (69%) was significantly higher than group 1 (48%) (P<0.05) and group 4 (47%) (P<0.05). There was no difference between group 3 (60%) and group 6 (P=0.2). From a clinical viewpoint, comparison of different electrocoagulation modes and pharmaceutical adhesion barriers is possible with standardised models.


2020 ◽  
Author(s):  
Kaicheng Li ◽  
Shuyue Wang ◽  
Xiao Luo ◽  
Qingze Zeng ◽  
Yerfan Jiaerken ◽  
...  

Abstract Background Along with Alzheimer’s disease (AD) continuum, AD neuropathologies propagate trans-neuronally, causing the memory circuit disorganization and memory deficit. However, no evidence supports the hypothesis in vivo to date. Methods Based on biological diagnosis criteria, we divided subjects into 5 groups by setting the CSF cutoff point at 192 pg/ml for Aβ 1-42 (A) and 23 pg/ml for P-tau 181 (T): Group 0, cognitively normal (CN) with normal Aβ 1-42 and P-tau 181 (A−T−); Group 1, CN with A+T−; Group 2, CN with A+T+; Group 3, mild cognitive impairments (MCI) with A+T+; Group 4, AD with A+T+. We defined the memory circuit as the hippocampus (HP), cingulum-angular bundles (CAB), and precuneus cortex, respectively representing the starting point, core connecting fiber, and connected downstream cortex. Then we assessed the HP subfields volume, CAB diffusion metric (whole tract-level and waypoint-wise), and precuneus volume. Finally, we correlated neuroimaging measures with cognitive and neuropathological data. Results Along AD continuum, HP subfields volume initially increased and then decreased, starting from the early stage (CN with A+T-). CAB integrity loss on both whole tract-level and waypoint-wise in MCI and AD with A+T+ and progressed along AD continuum. Regarding precuneus, we only found the decreased volume in MCI and AD with A+T+, with CN stage spared. Further, memory circuit structure impairment correlated with more AD neuropathology and worse memory profile. Conclusion Our results support the tau propagation theory in the memory circuit, suggested that the memory circuit impairments starting from the HP, then propagating to the downstream projection tract and cortex.


2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 214-214
Author(s):  
Rafael Nunez-Nateras ◽  
Erin N. Ferrigni ◽  
Naomi M. Gades ◽  
Erik P. Castle

214 Background: In our preliminary in vitro studies, we have demonstrated evidence of enhanced apoptosis and inhibition of cellular proliferation in both hormone sensitive and castrate resistant prostate cancer (PCa) cell lines using a combination of an antiandrogen (Bicalutamide) and a selective estrogen receptor modulator (Raloxifene). The aim of this study was to study the effect of the administration of these two drugs in in vivo models of castrate resistant PCa. Methods: In vivo model consisted on NCr Nude: Mice bearing s.c. human prostate (PC3 cell line) xenografts. Based on the treatment received, mice were divided into 5 groups as follows: Group 1: No drugs (control); Group 2: Bicalutamide 50mg; Group 3: Raloxifene 60 mg; Group 4: Combined administration of Bicalutamide 50 mg and Raloxifene 60 mg; Group 5 Combined administration of Bicalutamide 150 mg and Raloxifene 120 mg. A total of 10 mice where included in each group. All drugs dosages were converted to their equivalent in the mice. Drugs were administered by gavage technique to the mice once per day for a total of 14 days. Results: As expected, Bicalutamide administered alone causes minimal inhibition without reaching statistical significance (Group 2: 0.34 g Vs Group 1: 0.40 g; p=0.073). Although Raloxifene causes some marked growth inhibition, its effect is not statistically significant (Group 3: 0.31 Vs Group 1: 0.40 g; p=0.062). Bicalutamide and Raloxifene, when administered in combination, induced prominent growth inhibition in PC3 tumors when compared to the control group (Group 4: 0.26 g Vs Group 1: 0.40 g; p=0.038). Growth inhibition is significantly more evident when the drugs dosages are increased (Group 5: 0.17 g Vs Group 1: 0.40 g; p=0.024). Conclusions: The simultaneous administration of Bicalutamide and Raloxifene appears to have a synergistic effect on tumor growth inhibition in PC3 xenografts. The pathway(s) responsible for this observation may be independent of the androgen receptor as PC3 cells are AR negative and still affected by the combination over the drugs administered alone. Research is warranted to identify these potential pathways.


1997 ◽  
Vol 6 (5) ◽  
pp. 535-536 ◽  
Author(s):  
Hitoshi Horimoto ◽  
Masumi Nozawa ◽  
Norihiro Kokudo ◽  
Masatomo Nakao ◽  
Shigeki Takahashi ◽  
...  

We investigated the effects of monoclonal antibodies (mAbs) against lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) on intrasplenic allogenic and xenogenic hepatocyte transplantation (HCTx) to analbuminemic rats. Ten to 12-wk-old male Nagase's analbuminemic rats (RT1l) were used as recipients, Wistar/Shi rats (RTlk) were used as donors for allografts and BALB/C mice were used as donors for xenografts. The experimental groups were as follows: group 1, allo-HCTx (n = 7); group 2, allo-HCTx + antirat ICAM-1/antirat LFA-1 mAbs (1.0 mg/kg/day, for 7 days, respectively) (n = 6); group 3, xeno-HCTx (n = 5); group 4, xeno-HCTx + mAbs (antimouse LFA-1/antirat ICAM-1) (n = 5). group 5, xeno-HCTx + mAbs (antirat LFA-1/antimouse ICAM-1) (n = 5). Serum rat albumin levels were measured in groups 1 and 2, and serum mouse albumin levels were measured in groups 3, 4, and 5, as indicators of the function of grafted hepatocytes. In allotransplantation groups, the serum rat albumin levels in the mAbs-treated group were significantly higher than those in the control group for 6 wk after transplantation. In xenotransplantation groups, no increase in the serum mouse albumin levels was detected in any group.


2001 ◽  
Vol 281 (1) ◽  
pp. H75-H83 ◽  
Author(s):  
Navin Kumar Thakur ◽  
Toshio Hayashi ◽  
Daigo Sumi ◽  
Hatsuyo Kano ◽  
Taku Tsunekawa ◽  
...  

Male rabbits fed a 0.5% cholesterol diet for 8 wk were divided into three groups. Group 1 was hypercholesterolemic; group 2 was fed a regular diet for an additional 12 wk; and group 3 was fed a regular diet with simvastatin (5 mg · kg−1· day−1). Simvastatin treatment reduced the atherosclerotic area and total and esterified cholesterol concentrations in the thoracic aorta. Tone-related basal nitric oxide (NO) release was highest in group 3. Acetylcholine-induced, NO-dependent relaxation was improved in group 3 compared with group 2. Amount of endothelial nitric oxide synthase (eNOS) mRNA in vessels increased in group 1, compared with normal aorta, and decreased in group 2; however, it did not decrease in group 3. The amount of O[Formula: see text] released from vessels increased in group 1 and group 2 compared with normal rabbits; however, it decreased in group 3, especially in the endothelial cells. Peroxynitrite determined by nitrotyrosine staining decreased in group 3. Additionally, the arteries of rabbits fed a regular diet with or without simvastatin were investigated. The aorta from simvastatin-treated group showed increase of tone-related basal NO release and eNOS mRNA and decrease of O[Formula: see text]release. Taken together, upregulation of eNOS and decrease of O[Formula: see text] treatment were observed in vivo in the process of the sufficient stabilization of atheroma following simvastatin.


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