Cellular immune response to intrastriatally implanted allogeneic bone marrow stromal cells in a rat model of Parkinson's disease

Background

Marrow stromal cells (MSC), the non-hematopoietic precursor cells in bone marrow, are being investigated for therapeutic potential in CNS disorders. Although in vitro studies have suggested that MSC may be immunologically inert, their immunogenicity following transplantation into allogeneic recipients is unclear. The primary objective of this study was to investigate the cellular immune response to MSC injected into the striatum of allogeneic recipients (6-hydroxydopamine [6-OHDA]-hemilesioned rats, an animal model of Parkinson's disease [PD]), and the secondary objective was to determine the ability of these cells to prevent nigrostriatal dopamine depletion and associated motor deficits in these animals.

Methods

5-Bromo-2-deoxyuridine (BrdU) – labeled MSC from two allogeneic sources (Wistar and ACI rats) were implanted into the striatum of adult Wistar rats at the same time as 6-OHDA was administered into the substantia nigra. Behavioral tests were administered one to two weeks before and 16–20 days after 6-OHDA lesioning and MSC transplantation. Immunocytochemical staining for T helper and T cytotoxic lymphocytes, microglia/macrophages, and major histocompatibility class I and II antigens was performed on post-transplantation days 22–24. MSC were detected with an anti-BrdU antibody.

Results

Tissue injury due to the transplantation procedure produced a localized cellular immune response. Unexpectedly, both sources of allogeneic MSC generated robust cellular immune responses in the host striatum; the extent of this response was similar in the two allograft systems. Despite these immune responses, BrdU⁺ cells (presumptive MSC) remained in the striatum of all animals that received MSC. The numbers of remaining MSC tended to be increased (p = 0.055) in rats receiving Wistar MSC versus those receiving ACI MSC. MSC administration did not prevent behavioral deficits or dopamine depletion in the 6-OHDA-lesioned animals.

Conclusion

MSC, when implanted into the striatum of allogeneic animals, provoke a marked immune response which is not sufficient to clear these cells by 22–24 days post-transplantation. In the experimental paradigm in this study, MSC did not prevent nigrostriatal dopamine depletion and its associated behavioral deficits. Additional studies are indicated to clarify the effects of this immune response on MSC survival and function before initiating trials with these cells in patients with PD or other neurodegenerative disorders.     

Congenital cutaneous lymphadenoma

Cutaneous lymphadenoma is an uncommon benign neoplasm often considered to be an adamantinoid variant of trichoblastoma. Lesions present in both sexes, between 14 and 87 years of age, and are mainly located on the head and neck. Cases in children are rare and there is only 1 previous case of a congenital lymphadenoma. An 8‐year‐old Asian girl presented with a congenital lesion on her forehead comprising 4 pink papules, the largest 5 mm in diameter. Microscopy revealed a well‐circumscribed tumor within the dermis and subcutis comprising well‐demarcated epithelial lobules of basaloid and clear cells with subtle peripheral palisading, growing in a collagenous stroma but lacking retraction artefact. A relatively dense accompanying predominantly lymphocytic inflammatory cell infiltrate including both T‐cells (CD3+) and B‐cells (CD20+) permeated the nodules and spilled into the stroma. CD68+ histiocytes and CD1a+ Langerhans cells were moderately numerous. This is the second case of congenital lymphadenoma which—in spite of its rarity in childhood—widens the diagnostic possibilities of cutaneous lymphoepithelial tumors in children.     

Neurological disorders in complex humanitarian emergencies and natural disasters

Complex humanitarian emergencies include the relatively acute, severe, and overwhelming health consequences of armed conflict, food scarcity, mass displacement, and political strife. Neurological manifestations of complex humanitarian emergencies are important and underappreciated consequences of emergencies in populations worldwide. This review critically assesses the existing knowledge of the range of neurological disorders that accompany complex humanitarian emergencies and natural disasters in both the acute phase of crisis and the “long shadow” that follows. Ann Neurol 2010;68:282–294     

Impact of COVID-19 on U.S. and Canadian neurologists’ therapeutic approach to multiple sclerosis: a survey of knowledge,attitudes, and practices

Journal of Neurology - To report the understanding and decision-making of neuroimmunologists and their treatment of patients with multiple sclerosis (MS) during the early stages of the SARS-CoV-2...     

Dietitian-coached management in combination with annual endocrinologist follow up improves global metabolic and cardiovascular health in diabetic participants after 24 months

This 24 month study evaluated the effect of dietitian coaching combined with minimal endocrinologist follow up on the glycemic control and cardiovascular risks of diabetic participants, compared with conventional endocrinologist follow up. Participants with type 1 or type 2 diabetes were assigned to either the control group with conventional endocrinologist follow up (C; n = 50) or the dietitian-coached group (DC; n = 51) with on-site diabetes self-management education every 3 months combined with annual endocrinologist followup. Over the 24 month intervention, weight (-0.7 vs. +2.1 kg; p = 0.04), BMI (+0.3 vs. +0.7 kg/m(2); p = 0.009), and waist circumference (-1.3 vs. +2.4 cm; p = 0.01) significantly differed between the DC and control groups. HbA(1C) dropped significantly in participants of the DC versus the control group (-0.6% vs.-0.3%; p = 0.04). This was accompanied by improved overall energy intake (-548 vs. -74 kcal/day; p = 0.04). However, no link associated glycemic control to nutrient intake or intensiveness of pharmacotherapy. Coaching by a dietitian improves glycemic control and reduces certain cardiovascular risk factors in diabetic subjects, demonstrating that a joint dietitian-endocrinologist model of care provides a convenient strategy for cardiovascular risk management in the diabetic population.     

Medical conditions among Iraqi refugees in Jordan: data from the United Nations Refugee Assistance Information System

Objective

To determine the range and burden of health services utilization among Iraqi refugees receiving health assistance in Jordan, a country of first asylum.

Methods

Medical conditions, diagnosed in accordance with the tenth revision of the International classification of diseases, were actively monitored from 1January to 31December 2010 using a pilot centralized database in Jordan called the Refugee Assistance Information System.

Findings

There were 27 166 medical visits by 7642 Iraqi refugees (mean age: 37.4 years; 49% male; 70% from Baghdad; 6% disabled; 3% with a history of torture). Chronic diseases were common, including essential hypertension (22% of refugees), visual disturbances (12%), joint disorders (11%) and type II diabetes mellitus (11%). The most common reasons for seeking acute care were upper respiratory tract infection (11%), supervision of normal pregnancy (4%) and urinary disorders (3%). The conditions requiring the highest number of visits per refugee were cerebrovascular disease (1.46 visits), senile cataract (1.46) and glaucoma (1.44). Sponsored care included 31 747 referrals or consultations to a specialty service, 18 432 drug dispensations, 2307 laboratory studies and 1090 X-rays. The specialties most commonly required were ophthalmology, dentistry, gynaecology and orthopaedic surgery.

Conclusion

Iraqi refugees in countries of first asylum and resettlement require targeted health services, health education and sustainable prevention and control strategies for predominantly chronic diseases.     

A conservative treatment for plastic bronchitis in pediatric age

Plastic bronchitis is a rare disorder in pediatric age. This disease can cause life-threatening episodes. Broncoscopy plus bronchial lavage is considered the gold standard therapeutic technique. Knowledge of this disease is mandatory to perform correct diagnosis and provide prompt treatment. The authors report the history of a 5-year-old girl affected by plastic bronchitis who was successfully treated by a conservative therapy avoiding the traditional more invasive management.