Effects of Cannabis in Parkinson's Disease: A Systematic Review and Meta-Analysis.

The legalization of cannabis in many countries has allowed many Parkinson's disease (PD) patients to turn to cannabis as a treatment. As such there is a growing interest from the PD community to be properly guided by evidence regarding potential treatment benefits of cannabis. This systematic review and meta-analysis aims to compile the best available evidence to help guide patients and their family, clinicians and researchers make informed decisions. A systematic search of the literature was conducted in June 2021. Five randomized controlled studies and eighteen non-randomized studies investigated cannabis treatment in PD patients. No compelling evidence was found to recommend the use of cannabis in PD patients. However, a potential benefit was identified with respect to alleviation of PD related tremor, anxiety, pain, improvement of sleep quality and quality of life. Given the relative paucity of well-designed randomized studies, there is an identified need for further investigation, particularly in these areas.

PRES-like presentation in MOG antibody-related demyelination (MARD).

A 33-year-old male presented with a progressive four-week history of frontal headache and left visual field impairment. MRI brain confirmed bilateral, asymmetric, occipital vasogenic oedema, suggestive of posterior reversible encephalopathy syndrome (PRES). Serum testing for MOG antibodies was positive, confirming a diagnosis of MOG antibody-related demyelination (MARD). A similar PRES-like pattern of white matter inflammation has been reported previously in neuromyelitis optica spectrum disorder but has not previously been reported in MARD.

Development of Critical-size Abdominal Defects in a Rabbit Model to Mimic Mature Ventral Hernias.

BACKGROUND/AIM: Mesh hernioplasty is one of the most frequently performed procedures in the United States. Abdominal rigidity and chronic inflammation, among other factors, contribute to long-term complications including chronic pain, abdominal wall stiffness and fibrosis. Acute models do not replicate the chronic environment associated with most hernias, limiting the ability to improve products. The present study details development of a critical-size defect in rabbit abdominal wall for maturation into a chronic hernia to enable analysis of hernia repair devices in a realistic environment. MATERIALS AND METHODS: New Zealand White Rabbits were used to assess defect creation and mature hernia development through a period of 21-35 days. RESULTS AND CONCLUSION: Through this study, a critical-size defect was developed based on 3-cm full-thickness incision through musculature and peritoneum followed by simple skin closure and wound maturation, which was identified as a reliable procedure for creating defects presenting typical aspects of mature hernias including hernia ring and adhesions.

Injectable in situ forming controlled release implant composed of a poly-ether-ester-carbonate and applications in the field of chemotherapy.

Polymeric controlled delivery systems hold great promise in the field of modern medicine. Such technology has already been converted into commercially viable products in a myriad of fields. Chemotherapy is an example of such an area where constant efficacious levels of drug can greatly enhance clinical outcomes. The key to designing such therapies is the preparation of the proper delivery system. To this end, a series of bioresorbable polyether-ester-carbonate copolymers have been developed, which when combined with a diluent, are capable injection into the body and consistently forming a drug delivery depot. The study delineated here aimed at producing a more effective treatment of a common drug, paclitaxel, using the polymeric carrier. The polymer carrier system exhibited controlled release of paclitaxel both in vitro and in vivo. Drug concentrations were analyzed by high performance liquid chromatography and apoptotic activity was confirmed through flow cytometry. Relevant success was exhibited by the regression of tumor size following a multiple injection treatment regimen in a murine xenograft model. This multiple injection treatment shows promising results when compared to the traditional paclitaxel paradigm of a single injection for a period of 3 weeks.

Absorbable microparticulate cation exchanger for immunotherapeutic delivery.

An absorbable microparticulate cation exchanger was synthesized as a versatile carrier for biologically active proteins. In this work, acid-terminated polyglycolide (or polyglycolic acid) microparticulates (PG-MP) were surface modified for either sustained release of cytokines or as a platform for immunomodulation. The intended goal was to achieve in situ recruitment/maturation of dendritic cells and activation of T cells for tumor immunotherapy. PG-MP were prepared with a volume weighted mean diameter of 7.02 micro (range: 2.09-14.58 micro). Accessible carboxylic acid groups were determined to be 0.3 mmol/g with a corresponding zeta potential of -21.87 mV in phosphate-buffered saline. Under low magnification, scanning electron microscopy (SEM) revealed a highly textured surface due to processing from repetitive jet milling. However, a moderately porous architecture was noted at higher magnification. Electron spectroscopy for chemical analysis was used to characterize the PG-MP surface before and after adsorption of human granulocyte-macrophage colony stimulating factor (GM-CSF). Adsorption of GM-CSF on PG-MP (PG-GMCSF) resulted in a modest increase in the surface atomic concentration of nitrogen (0.97%). Pretreating the surface with poly-L-lysine (PG/Lys-GMCSF) prior to adding GM-CSF produced a nearly threefold increase in the surface nitrogen concentration (4.20% compared to 1.47%). This manipulation not only increased loading content, but also prolonged the release of GM-CSF released from 6 days to 26 days. ESCA on the post-release PG-MP samples (PG-GMCSF and PG/Lys-GMCSF) revealed a similar residual surface nitrogen concentration (2.26% vs. 2.35%). The observation was consistent with irreversibly adsorbed GM-CSF. It is postulated that irreversibly bound GM-CSF is released over time as a function of microparticulate degradation. Biological activity of released GM-CSF was confirmed by the proliferation of a GM-CSF-dependent cell line (TF-1) in the presence of microparticulates. PG-MP mediated activation of T cells was achieved through irreversible adsorption of either antimouse cd3 plus antimouse cd28 monoclonal antibodies (alpha-cd3/cd28-MP) or antihuman CD3 plus antihuman CD28 monoclonal antibodies (alpha-CD3/CD28-MP) on PG-MP. Irreversibly adsorbed antibodies were capable of activating both resting mouse and human T cells. Intracellular flow cytometry on mouse T cells revealed that nearly 50% of the activated cells produced interferon-gamma (IFN-gamma). This was consistent with a TH-1 or cell-mediated response. In vivo efficacy was evaluated in a mouse flank tumor model showing a significant antitumor effect both alone and in combination. Combination therapy was most effective at preventing tumor implantation (8/8 mice) and was able induce tumor regression (4/7 mice) and/or stable disease (3/7 mice) in a regression model. In these studies, immunohistochemistry was used to confirm local recruitment of dendritic cells. In conclusion, the PG-MP represents a novel absorbable cation exchanger that can be readily manipulated to deliver biologically active proteins for immunotherapy.

Development of novel substrates for tumor immunotherapy.

Acid-terminated polyglycolide microparticles (PG-MP) were prepared as a versatile substrate that could be surface-modified for either immobilization of anti-cd3 and anti-cd28 mAb to activate T cells or sustained release of granulocyte-macrophage colony stimulating factor (GM-CSF) for dendritic cell (DC) recruitment and maturation. PG-MP were prepared with a volume-weighted mean diameter of 56 or 57 microm. Accessible carboxylic acid group concentration was determined by potentiometric titration to be 0.3 mmole/g and corresponded to a zeta potential of -21.87 mV. PG-MP immobilized with either anti-human CD3/CD28 or anti-mouse cd3/cd28 induced significant proliferation of T cells. Intracellular flow cytometry in activated mouse T cells was significant for IFN-gamma, but not IL-4. Microparticles surface-modified for GM-CSF release were prepared from either PG-MP or PG pre-treated with poly-L-lysine (PG-Lys) to manipulate surface charge. GM-CSF released from PG-Lys-MP was observed for up to 26 days. The biologic activity of released GM-CSF was confirmed by using a h-GM-CSF-dependent cell line. The efficacy of the alpha-cd3/cd28-MP and GMCSF-MP was studied in a syngeneic mouse tumor prevention and regression model. Co-injection of Meth A fibrosarcoma cells with alpha-cd3/cd28-MP and GMCSF-MP completely prevented tumor implantation (0/24). The regression model showed complete tumor regression in four of seven animals and stable disease in three of seven. In the latter study, a dramatic level of DC infiltration was observed compared to controls.