Animal models of spontaneous intracerebral hemorrhage

Objectives: Intracerebral hemorrhage (ICH) is a type of stroke that results in significant mortality and morbidity. Currently there is no definitive treatment for this disease. The paucity of animal models that reflect the heterogeneity of this spontaneous human disease could be the reason. Methods: In this review, we searched the literature for animal models of spontaneous ICH and found eight relevant papers.

Results: Two were related to hypertension and six were related to cerebral amyloid angiopathy (CAA). One model used double transgenic mice overexpressing human renin and angiotensinogen which caused the mice to be hypertensive. Induction of ICH, however required addition of a high salt diet and nitric oxide synthase inhibition. Another mouse model of hypertension employed subcutaneous angiotensin II infusion and nitric oxide synthase inhibition plus acute injections of angiotensin to further elevate blood pressure. Five CAA models were in transgenic mice overexpressing amyloid precursor protein. One relied on the natural development of CAA in squirrel monkeys.

Conclusions: While all of the spontaneous ICH models have some advantages, the disadvantages include the sporadic time of onset of ICH and variability in size and location of ICH. Since there are no known efficacious treatments for ICH, it is not known if findings in the animal models will find treatments that are effective in humans.     

Rekonstruktion von Segmentdefekten der langen Röhrenknochen

Surgery of malignant tumors and the subsequent outcome after treatment of complicated fracture situations of long bones often result in major bone defects. In addition to bridging of defects and stabilization with allogenic implants, defect reconstruction by callus distraction with segment transport and vascularized free fibula transfer are the procedures of choice for defect reconstruction in long bones. The heterogeneity of the causes of large bone defects and specific comorbidities of the patients require a differentiated approach. The indications and characteristics of the various surgical approaches and current developments in procedures for reconstruction of large defects in long bones are presented.     

Low-energy laser therapy application on knee joints as an auxiliary treatment in patients with polyarticular juvenile idiopathic arthritis: a dual-arm randomized clinical trial

Lasers in Medical Science - Patients with juvenile idiopathic arthritis (JIA) always experience persistent pain and stiffness which induces muscle weakness, fatigue, and functional limitations....     

Incisional hernia repair after kidney transplantation in a tertiary high-volume center: outcomes from a 10-year retrospective cohort study

International Urology and Nephrology - Incisional hernia (IH) after Kidney Transplantation (KT) is a challenging complication due to both technical reasons and patients’ complexity. Data...     

In vivo monitoring of implant osseointegration in a rabbit model using acoustic sound analysis

Implant osseointegration can currently only be assessed reliably post mortem. A novel method that relies on the principle of acoustic sound analysis was developed to enable examination of the longitudinal progress of osseointegration. The method is based on a magnetic sphere inside a hollow cylinder of the implant. By excitation using an external magnetic field, collision of the sphere inside the implant produces a sound signal. Custom‐made titanium implants equipped thusly were inserted in each lateral femoral epicondyle of 20 New Zealand White Rabbits. Two groups were investigated: Uncoated, machined surface versus antiadhesive surface; and calcium phosphate‐coated surface versus antiadhesive surface. The sound analysis was performed postoperatively and weekly. After 4 weeks, the animals were euthanized, and the axial pull‐out strengths of the implants were determined. A significant increase in the central frequency was observed for the loose implants (mean pull‐out strength 21.1 ± 16.9 N), up to 6.4 kHz over 4 weeks. In comparison, the central frequency of the osseointegrated implants (105.2 ± 25.3 N) dropped to its initial value. The presented method shows potential for monitoring the osseointegration of different implant surfaces and could considerably reduce the number of animals needed for experiments. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:606–612, 2014.     

Morbidity and Mortality in the Thirty-Day Period Following Total Hip Arthroplasty: Risk Factors and Incidence

The study sought to ascertain the incidence rates and risk factors for 30-day post-operative complications after primary total hip arthroplasty (THA). Complications were categorized as systemic or local and subcategorized as major or minor. There were 17,640 individuals who received primary THA identified from the 2006-2011 ACS NSQIP. The mortality rate was 0.35% and complications occurred in 4.9%. Age groups ≥ 80 years (P <0.001) and 70-79 years old (P = 0.003), and renal insufficiency (P = 0.02) best predicted mortality. Age ≥80 years (P <0.001) and cardiac disease (P = 0.01) were the strongest predictors of developing any postoperative complication. Morbid obesity (P <0.001) and operative time > 141 minutes (P <0.001) were strongly associated with the development of major local complications.     

Surgical delivery of drug releasing poly(lactic-co-glycolic acid)/poly(ethylene glycol) paste with in vivo effects against glioblastoma

Introduction

The median survival of patients with glioblastoma multiforme (astrocytoma grade 4) remains less than 18 months despite radical surgery, radiotherapy and systemic chemotherapy. Surgical implantation of chemotherapy eluting wafers into the resection cavity has been shown to improve length of survival but the current licensed therapy has several drawbacks. This paper investigates in vivo efficacy of a novel drug eluting paste in glioblastoma.

Methods

Poly(lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) self-sintering paste was loaded with the chemotherapeutic agent etoposide and delivered surgically into partially resected tumours in a flank murine glioblastoma xenograft model.

Results

Surgical delivery of the paste was successful and practical, with no toxicity or surgical morbidity to the animals. The paste was retained in the tumour cavity, and preliminary results suggest a useful antitumour and antiangiogenic effect, particularly at higher doses. Bioluminescent imaging was not affected significantly by the presence of the paste in the tumour.

Conclusions

Chemotherapy loaded PLGA/PEG paste seems to be a promising technology capable of delivering active drugs into partially resected tumours. The preliminary results of this study suggest efficacy with no toxicity and will lead to larger scale efficacy studies in orthotopic glioblastoma models.     

Congestive Heart Failure: A Case of Protein Misfolding

This article describes an interesting case of a patient presenting with congestive heart failure found to have restrictive cardiomyopathy with initial laboratory evaluation showing hypogammaglobuminemia without a monoclonal band on serum and urine electrophoresis. This case highlights the clinically significant cardiac manifestation caused by protein misfolding, a defect in protein homeostasis. In addition, the utility of a relatively newer laboratory test, serum free light chains as well as the importance of clinical and pathophysiologic correlation is also discussed. We present a relatively uncommon cause of heart disease, cardiac amyloidosis in a patient with a systemic plasma cell dyscrasia, and multiple myeloma.     

Transgenic angiotensin-converting enzyme 2 overexpression in vessels of SHRSP rats reduces blood pressure and improves endothelial function

Rat models of hypertension, eg, spontaneously hypertensive stroke-prone rats (SHRSP), display reduced angiotensin-converting enzyme 2 (ACE2) mRNA and protein expression compared with control animals. The aim of this study was to investigate the role of ACE2 in the pathogenesis of hypertension in these models. Therefore, we generated transgenic rats on a SHRSP genetic background expressing the human ACE2 in vascular smooth muscle cells by the use of the SM22 promoter, called SHRSP-ACE2. In these transgenic rats vascular smooth muscle expression of human ACE2 was confirmed by RNase protection, real-time RT-PCR, and ACE2 activity assays. Transgene expression leads to significantly increased circulating levels of angiotensin-(1-7), a prominent product of ACE2. Mean arterial blood pressure was reduced in SHRSP-ACE2 compared to SHRSP rats, and the vasoconstrictive response to intraarterial administration of angiotensin II was attenuated. The latter effect was abolished by previous administration of an ACE2 inhibitor. To evaluate the endothelial function in vivo, endothelium-dependent and endothelium-independent agents such as acetylcholine and sodium nitroprusside, respectively, were applied to the descending thoracic aorta and blood pressure was monitored. Endothelial function turned out to be significantly improved in SHRSP-ACE2 rats compared to SHRSP. These data demonstrate that vascular ACE2 overexpression in SHRSP reduces hypertension probably by locally degrading angiotensin II and improving endothelial function. Thus, activation of the ACE2/angiotensin-(1-7) axis may be a novel therapeutic strategy in hypertension.