<p>This dissertation details the creation, validation, and characterization of a porcine ex-vivo culture model to study subcuteneous tissue. The viability of the model was assessed over seven days of culture by digestion and the proliferation and death of cells was monitored by immunohistochmeical labelling and image analysis. The model was then used in a timecourse proteomics experiment to characterize the effect of culture on subcutaneous proteome. The model was then compared to a commercially available human ex-vivo model with respect to viability and changes to the subcutaneous proteome. </p>

Accumulation of cervical and chin subcutaneous adipose tissues (SAT) represent known phenotypes of obesity. We aimed to evaluate the sensitivity of these fat storages to long-term weight-loss directed lifestyle-intervention and to assess their relations to bodily-adiposity, insulin-resistance, and cardiometabolic risk; We randomly assigned 278 participants with abdominal-obesity/dyslipidemia to low-fat or Mediterranean/low-carbohydrate diets +/− physical-activity. All participants underwent an 18 month whole-body magnetic resonance imaging follow-up, from which we assessed cervical and chin SAT-areas; Participants (age = 48 years; 90% men; body-mass-index = 30.9 kg/m2) had an 18-month adherence-rate of 86%. Cervical-SAT and chin-SAT decreased after 6-months (−13.1% and −5.3%, respectively, p < 0.001). After 18-months only cervical-SAT remained decreased compared to baseline (−5%, p < 0.001). Cervical and chin-SAT 18-month changes were associated with changes in weight (r = 0.70, r = 0.66 respectively; <0.001 for both) and visceral-adipose-tissue (VAT; r = 0.35, r = 0.42 respectively; <0.001 for both). After adjustment to VAT, waist-circumference, or weight-changes, chin-SAT 18-month reduction was associated with favorable changes in fasting-glucose (β = 0.10; p = 0.05), HbA1c (β = 0.12; p = 0.03), and homeostasis-model-assessment-of-insulin-resistance (β = 0.12; p = 0.03). Cervical-SAT 18-month reduction was associated with decreased triglycerides (β = 0.16; p = 0.02) and leptin (β = 0.19; p = 0.01) independent of VAT; Cervical and chin-SATs are dynamic fat depots that correspond with weight-loss and are associated with changes in cardiometabolic profile. In long-term, chin-SAT displays a larger rebound compared with cervical-SAT. Chin-SAT accumulation is associated with in insulin-resistance, independent of central obesity. (ClinicalTrials identifier NCT01530724)

Introduktion: I Sverige har det uppmätts att 27% av befolkningen har en luftvägsallergi. Dessa behandlas främst med symtomlindrande läkemedel men när detta inte räcker till kan allergenspecifik immunterapi (ASIT) övervägas. Denna behandling kan ges antingen sublingualt eller med subkutana injektioner. Den första studien om ASIT publicerades 1911 och sedan dess har många studier gjorts angående dess effekter. Syfte: Syftet med studien var att undersöka patienters upplevelser av subkutan immunterapi (SCIT). De områden som belystes var upplevelsen av information och kommunikation, psykisk och fysisk påverkan av biverkningar samt hur behandlingen inverkar på vardagen. Metod: En kvalitativ studiedesign användes och data samlades in med hjälp av semistrukturerade intervjuer. Ett bekvämlighetsurval gjordes på en allergimottagning i Mellansverige och tio personer intervjuades. Resultat: Behandlingen påverkade somliga delar av vardagen i viss mån, till exempel att det är tidskrävande och att den fysiska aktiviteten blir begränsad under behandlingsdagen. En del biverkningar förekom, främst allmänna och lokala. Dessa hade viss påverkan på vardagen relaterat till exempelvis trötthet och koncentrationssvårigheter. Kontakten med mottagningen upplevdes positivt och informationen som erhölls inför behandlingsstart upplevdes som tillräcklig. Dock framkom att informationen kring allvarligare biverkningar inte nått fram till alla. Slutsats: Både de upplevda biverkningarna och behandlingen som helhet hade en viss påverkan på patienternas vardag. Kommunikationen och informationen från vården upplevdes överlag positivt. Vidare forskning inom området behövs för att kunna avgöra om dessa resultat är överförbara till en bredare population. / Introduction: It has been measured that 27% of the population in Sweden has a respiratory allergy. Primarily this is treated symptomatically with medication but in cases where this do not work, allergen specific immunotherapy (ASIT) can be considered. ASIT can be administered either sublingually or subcutaneously. The first study acknowledging ASIT was published in 1911 and since then many studies have been performed regarding its effects.      Aim: The aim of this study was to examine patients experiences of subcutaneous immunotherapy (SCIT). This included how patients experienced information and communication, how side-effects affected patients physically and psychologically and how the treatment affected the patients’ everyday life.  Methods: A qualitative study design was used and data was collected with semi-structured interviews. A convenience sample was made at an allergy reception in central Sweden and ten people were interviewed. Results: Parts of the patients’ everyday life were affected to some extent, for example because the treatment is time consuming and that the physical activity has to be limited during the same day as the injection is given. Some side-effects occurred, primarily general and local ones. These affected the everyday life in the sense that the patients felt tired and experienced difficulty concentrating. The contact with the reception was described in a positive manner and the information received before starting treatment was described to be enough. Although the information regarding serious side-effects had not been reached by everyone. Conclusion: Both the experienced side-effects and the treatment in its whole had a certain impact on the patients’ everyday life. The patients described the communication and the information in a positive way. More studies need to be performed in this field to be able to determine whether these results are transferable to a broader population.

Na engenharia de tecidos os biomateriais são usados tanto para induzir a formação óssea no tecido adjacente quanto agir como matriz temporária de células e outros agentes. Compósitos biodegradáveis a base de hidroxiapatita, colágeno e quitosana foram preparados como arcabouços para permitir a regeneração óssea. Este estudo teve como objetivo avaliar a toxicidade celular in vitro de novos compósitos de substituição óssea e o seu comportamento biológico após implantação subcutânea no processo de remodelação e cicatrização tecidual. Foram confeccionadas mantas a base de hidroxiapatita (HA), obtida por desproteinização e calcinação do osso bovino, colágeno (Col), obtido por tratamento alcalino do tendão bovino e quitosana (Qui), extraída do gládio de lula, nas seguintes proporções: B1) HA (mistura de partículas <0,2 mm e entre 0,2 e 1,18 mm, proporção 1:1) + Blenda (Col 1% + Qui 0,5%, proporção 1:1), proporção HA:Blenda 1:5; B2) HA (mistura de partículas <0,2 mm e entre 0,2 e 1,18 mm, na proporção 1:1) + Col 1%, proporção HA:Col 1:5; B3) HA (partículas <0,2 mm) + Col 1%, na proporção 1:5. O teste de citotoxicidade in vitro foi realizado pelo método de difusão de extrato em solução (brometo de tetrazolio - MTT). Os biomateriais descritos acima foram avaliados juntamente com o controle positivo (látex), sendo que todos foram submetidos a procedimentos de extração de acordo as normas da ISO10993-5. O meio de cultura foi utilizado como controle negativo. Foram utilizadas duas linhagens celulares: células tumorais de laringe humana HEp (ATCC-CCL-23) e células normais de rim de macaco verde africano (Cercopithecus aethiops) VERO (n=3). A citotoxicidade foi avaliada em um espectrofotômetro (absorbância de 570nm). No teste de biocompatibilidade as amostras foram implantadas no subcutâneo da região dorsal de 51 ratos Wistar. Histomorfometria de espessura e qualidade da cápsula fibrosa, interface implante-tecido, infiltrado inflamatório e crescimento celular interno foram realizados aos 3, 7 e 28 dias após cirurgia (n=5). Imunohistoquímica foi realizada para caracterizações adicionais do infiltrado de macrófagos. No teste de citotoxicidade as linhagens celulares mostraram resultados semelhantes. Não houve diferença entre os compósitos e o controle negativo. Foi demonstrado que os compósitos avaliados não apresentaram efeitos tóxicos em comparação ao controle positivo. No teste subcutâneo a qualidade e a espessura da cápsula não apresentaram diferenças significantes entre os biomateriais e os períodos de implantação. A resposta celular inflamatória aos 7 dias foi mais intensa no biomaterial B1, seguido pelo biomaterial B2 e B3. Uma baixa reação de corpo estranho foi observada em todos os biomateriais, caracterizada pela presença de poucos macrófagos. Ocorreu um intenso crescimento celular no interior do biomaterial B3 aos 28 dias. A análise histológica sugere que esses biomateriais são bem tolerados com baixa reação tecidual inflamatória. Concluímos que os três biomateriais avaliados não apresentaram evidências de citotoxicidade in vitro e, in vivo, mostraram uma boa biocompatibilidade. Esses materiais mostraram-se bons candidatos a matrizes para engenharia de tecidos e enxertos para regeneração óssea. / The biodegradable hydroxyapatite / chitosan / collagen composites of similar composition of the normal human bone were prepared as a biomimetic scaffold for bone replacement and regeneration. The aim of the present study was to evaluate the in vitro cytotoxicity of three new bone grafts and the influence of these synthetic grafts on the inflammatory response and remodeling of connective tissue during wound-healing process. Three biomaterials were developed: B1 = hydroxyapatite (particles size <0,2 mm + between 0,2 and 1,18 mm) / collagen 1% / chitosan 0.5%; B2 = hydroxyapatite (particles size <0,2 mm + between 0,2 and 1,18 mm) / collagen 1% and B3 = hydroxyapatite (particles size <0,2 mm) / collagen 1%. These biomaterials were investigated using a tetrazolium-based calorimetric assay (MTT assay). Latex was used as positive control and the culture medium as a negative control. Two cell lines were used to evaluate the effect of cell type on the toxicity results: human tumor cells HEp-2 (ATCC-CCL23) and monkey normal cells (VERO). Extracts from the biomaterials were obtained according to ISO 10993-12 standards. The cytotoxicity was assessed in a spectrophotometer (the absorbance was read at 570 nm). There were two independent experiments in triplicates. All values were expressed as mean values \'+ OU -\' standard deviation. In the biocompatibility test the samples were implanted subcutaneously in the dorsal lumbar region of 51 Wistar rats. Histomorphometric evaluation of capsule thickness, capsule quality, implant-tissue interface, infiltrate / inflammation and cellular growth within implant was performed 3, 7 and 28 days post-operatively (n=5). Immunohistochemistry was performed for further characterization of the macrophages infiltrate. In cytotoxicity test the cell lines showed similar results. There is no difference in values between the composites and negative control. The values of composites were significant different than the positive control. It was showed that none of the tested composites presents toxic effects for the cell lines evaluated in comparison with positive control. In the subcutaneous test the capsule thickness and capsule quality didn\'t show significant differences between the biomaterials and time of implantation. The biomaterial B1 showed significant difference in inflammatory cellular response than B2 and B3 at 7 days. A low ongoing foreign body reaction was observed in all biomaterials characterized by infiltration of few macrophages. A significant cellular growth within the B3 was observed at 28 days. Histological analysis suggested that the biomaterials were well tolerated with low inflammatory response. According to this study, the three bone grafts evaluated showed no evidence of cytotoxicity and good biocompatibility which makes them suitable candidates to design of bone replacement graft material.

Introdução. A hidrocefalia é uma doença de complexa fisiopatologia, que não só afeta a dinâmica do líquido cefalorraquidiano (LCR), mas também outras estruturas do sistema nervoso central, e consequentemente pode trazer sequelas graves em crianças. Sua fisiopatologia, principalmente no nível bioquímico-celular, ainda é pouco conhecida. Objetivos. Avaliar aspectos clínicos (ganho ponderal, comportamento motor e memória), radiológicos (razão ventricular e transferência de magnetização), histopatológicos (astrocitose reativa e proliferação celular na matriz germinativa) e bioquímicos (presença de interleucinas inflamatórias no líquor) na fase aguda da hidrocefalia experimental induzida por caulim e o efeito do tratamento com derivação adaptada (ventrículo-subcutânea). Materiais e métodos. Utilizaram-se ratos Wistar com 7 dias de vida, que foram divididos em três grupos: controle sem injeção de caulim (n = 5), hidrocefálico sem tratamento (n=17), e hidrocefálico tratado com derivação ventrículo-subcutâneo (DVSC), a partir do 7o dia pós-indução (n=24). Os animais dos grupos hidrocefálicos tratado e não tratado receberam uma injeção de caulim a 15% na cisterna magna, para a indução da hidrocefalia, no 7o dia do estudo. Resultados. O ganho de peso foi semelhante nos grupos hidrocefálicos mas menor que no grupo controle. Animais tratados e não tratados exibiram desempenho inferior aos controles no comportamento motor pelo teste Open Field, ao passo que o desempenho no teste de memória foi melhor no grupo tratado. A DVSC reduz drasticamente as dimensões ventriculares, porém não reverte a desmielinização causada pela hidrocefalia, como visto na avaliação por ressonância magnética. Da mesma forma, os processos de astrocitose reativa (que aumenta com a hidrocefalia) e proliferação na matriz germinativa (que se reduz) não se alteram após o tratamento com a DVSC. A hidrocefalia aumenta os níveis liquóricos das interleucinas 1? e 6 e TNF-?, que retornam ao normal após o tratamento. Conclusões. O tratamento com a DVSC foi eficaz (considerando-se a redução ventricular) e trouxe benefícios comportamentais e celulares, porém não foi suficiente para alterar o curso dos processos de injúria e reparação celular cerebral já estabelecidos. Depreende-se que há participação de mecanismos inflamatórios neste modelo de hidrocefalia experimental a partir do achado de aumento de interleucinas inflamatórias no líquor / Introduction. Hydrocephalus is a complex disease, which affects not only cerebrospinal fluid dynamics, but also other cerebral structures, and therefore may result in severe disability for children. Its pathophysiology is still widely unknown, especially on a cellular-biochemical level. Objectives. Assessment of clinical (weight gain, behavior), radiological (ventricular index and magnetization transfer ratio), histopathological (reactive astrocytosis and cell proliferation over the germinal matrix) and biochemical (dosage of inflammatory interleukins) aspects of acute kaolin-induced experimental hydrocephalus and the effects of the treatment with an adapted shunt (ventricular-subcutaneous). Methods. 7-day-old Wistar rats were divided into three groups: untreated hydrocephalic (n=17), hydrocephalic treated with shunt on the 7th day after induction (n=24) and controls (n=5). Hydrocephalic animals, both treated and untreated, were injected with a 15% kaolin solution on the cisterna magna, to produce hydrocephalus. Results. Weight gain was similar on both hydrocephalic groups but lower than in controls. Motor behavior was also worse than controls for both groups, but treated animals showed better memory performance than their untreated counterparts. Shunting drastically reduces ventricular size, even though it does not reverse demyelination caused by hydrocephalus, as seen in magnetic resonance scanning analyses. Likewise, reactive astrocytosis and cell proliferation at the germinal matrix do not change after treatment. Interleukins 1? and 6 and TNF-? levels are raised in hydrocephalic rats and return to normal after shunting. Conclusions. The ventricular-subcutaneous shunt for treatment of kaolininduced hydrocephalus in rats is effective (i.e, reduces ventricular size) and has clinical and histological benefits, but is not enough to change the evolution of previously established injury and cellular reparation processes on the hydrocephalic brain. The finding of raised inflammatory interleukins on the cerebrospinal fluid suggests a role for inflammation in the pathogenesis of this experimental model of hydrocephalus

<p>The amyloidoses are biochemically heterogeneous diseases with patholophysiologic deposits of various proteins. Amyloid deposits can occur either localized to one organ or tissue or as part of a systemic disease with deposits in many different tissue. The clinical course, prognosis and therapy are different for each type of amyloidosis and therefore a type specific diagnosis is demanded as early as possible. We describe a method for typing of the most common systemic amyloidoses based on Western blot analysis combined with specific</p><p>in- house antibodies, using subcutaneous fat biopsies. We found that the method is reliable and easy to perform and the tissue sample needed is obtained by minor surgery.</p><p>In the aortic intima amyloid deposits are often associated with atherosclerosis plaques. In our study we also investigated the prevalence of intimal amyloid from 10 patients age 58-94, amyloid deposits were present in 50% of the cases.</p> / <p>Amyloidos är ett sjukdomstillstånd där proteiner som normalt är lösliga i kroppen felveckas och formar långa olösliga fibriller som ansamlas i vävnader och organ såsom t.ex. hjärta, hjärna och lever. Det finns cirka 25 proteiner som kan ge upphov till amyloidos. Man kan skilja på två huvudgrupper av amyloidos, systemisk och lokaliserad. Vid lokal amyloidos kan inlagringar förekomma i specifika vävnader vid framför allt vissa åldersberoende sjukdomar som t.ex. Alzheimers sjukdom. Vid systemisk amyloidos förekommer inlagringar i praktiskt taget alla vävnader. Symtomatologin vid systemisk amyloidos är variabel och sjukdomsbilden kan vara svårtolkad men tidig och specifik diagnostik ger möjlighet till riktad terapi mot den bakomliggande sjukdomen. Syftet med denna studie var att utvärdera en Western blot metod som använts för typning av vanligaste formerna av systemisk amyloidos. De slutsatser som nåtts är att denna metod är snabbt, pålitligt och enkel att utföra. Diagnos erhölls med finnålsbiopsi av bukfettvävnad som är enkel, snabb och billig metod med liten risk för patienternas hälsa. Vi lyckades också med hjälp av immunhistokemisk infärgning titta på prevalens av amyloid i aortas intima.</p>

No description available.

1,25-dihydroxyvitamin D3 (Vitamin D) is a potent immunomodulator capable of generating regulatory T cells (Tregs) and contributing to immune tolerance. Additionally, vitamin D has been shown to promote mucosal immunity when used as a vaccine adjuvant. We show here that pretreatment of an area of skin with the synthetic vitamin D analog calcipotriol combined with transcutaneous immunization results in the induction of CD4⁺CD25⁺ Tregs capable of inhibiting the elicitation of a contact hypersensitivity response. We also demonstrate that topical calcipotriol has significant effects on the immune response to subcutaneously injected vaccines, and compare it with another common topical immunosuppressant, the corticosteroid betamethasone-17-valerate (BMV). Functionally, calcipotriol and BMV treatment both result in the suppression of CD8⁺ T cell priming in response to subcutaneous vaccination, despite the topical co-administration of the potent Th1 inducing TLR9 agonist unmethylated CpG DNA. The effects of calcipotriol on the humoral response are subtler as we observe marginally increased production of antigen-specific IgG1 immunoglobulins along with a strong suppression of the IgG2a isotype. This is in contrast to pretreatment with BMV, which instead suppresses the production of IgG1 and IgA antibodies. In the draining lymph nodes of calcipotriol treated animals, we see no change in the percentage of Foxp3⁺ CD4⁺ T cells post-immunization, but show that tolerance is transferable with the adoptive transfer of CD4⁺CD25⁺ cells. Despite a decrease in the percentage of antigen-bearing APCs in the DLN of calcipotriol treated animals, the DCs maintain high expression of co-stimulatory markers and can induce CD4⁺ T cell proliferation ex vivo. Our data indicate that calcipotriol has distinct effects on immune responses to subcutaneous vaccines consistent with its role as an immunomodulator, although the mechanism(s) through which it is acting remain unclear. We believe that further research is warranted into its potential use as part of a treatment modality for allergy and autoimmune disorders.

The incidence of Type 1 diabetes is growing yearly. Worryingly, the aetiology of the disease is inconclusive. What is known is that the total number of affected individuals, as well as the severity and number of associated complications are growing for this chronic disease. With increasing complications due to severity, length of exposure, and poor control, the disease is beginning to consume an increasingly major portion of healthcare costs to the extent that it poses major economic risks in several nations. Research has shown that intensive insulin therapy aimed at certain minimum glycosylated haemoglobin threshold levels reduces the incidence of complications by up to 76% compared to conventional insulin therapy. Moreover, the effects of such intensive therapy regimes over a 6.5y duration persists for at least 10y after, a so called metabolic memory. Thus, early intervention can slow the momentum of complications far more easily than later intervention. Early, safe, intensive therapy protocols offer potential solutions to the growing social and economic effects of diabetes. Since the 1970s, the artificial endocrine pancreas has been heralded as just this type of solution. However, no commercial product currently exists, and ongoing limitations in sensors and pumps have resulted in, at best, modest clinical advantages over conventional methods of insulin administration or multiple daily injection. With high upfront costs, high costs of consumables, significant complexity, and the extensive infrastructure and support required, these systems and devices are only used by 2-15% of individuals with Type 1 diabetes. Clearly, there is an urgent need to address the large majority of the Type 1 diabetes population using conventional glucose measurement and insulin administration. For these individuals, current conventional or intensive therapies are failing to deliver recommended levels of glycaemic control. This research develops an understanding of clinical glycaemic control using conventional insulin administration and glucose measurement techniques in Type 1 diabetes based on a clinically validated in silico virtual patient simulation. Based on this understanding, a control protocol for Type 1 diabetes that is relatively simple and clinically practical is developed. The protocol design incorporates physiological modelling and engineering techniques to adapt to individual patient clinical requirements. By doing so, it produces accurate, patient-specific recommendations for insulin interventions. Initially, a simple, physiological compartmental model for the pharmacokinetics of subcutaneously injected insulin is developed. While the absorption process itself is subject to significant potential variability, such models enable a real-time estimation of plasma insulin concentration. This information would otherwise be lacking in the clinical environment of outpatient Type 1 diabetes treatment due to the inconvenience, cost, and laboratory turnaround for plasma insulin measurements. Hence, this validated model offers significant opportunity to optimise therapy selection. An in silico virtual patient simulation tool is also developed. A virtual patient cohort is developed on patient data from a representative cohort of the broad diabetes population. The simulation tool is used to develop a robust, adaptive protocol for prandial insulin dosing against a conventional intensive insulin therapy, as well as a controls group representative of the general diabetes population. The effect on glycaemic control of suboptimal and optimal, prandial and basal insulin therapies is also investigated, with results matching clinical expectations. To gauge the robustness of the developed adaptive protocol, a Monte Carlo analysis is performed, incorporating realistic and physiological errors and variability. Due to the relatively infrequent glucose measurement in outpatient Type 1 diabetes, a method for identifying the diurnal cycle in effective insulin sensitivity and modelling it in retrospective patient data is also presented. The method consists of identifying deterministic and stochastic components in the patient effective insulin sensitivity profile. Circadian rhythmicity and sleep-wake phases have profound effects on effective insulin sensitivity. Identification and prediction of this rhythm is of utmost clinical relevance, with the potential for safer and more effective glycaemic control, with less frequent measurement. It is thus a means of further enhancing any robust protocol and making it more clinically practical to implement. Finally, this research presents an entire framework for the realistic, and rapid development and testing of clinical glycaemic control protocols for outpatient Type 1 diabetes. The models and methods developed within this framework allow rapid and physiological identification of time-variant, patient-specific, effective insulin sensitivity profiles. These profiles form the responses of the virtual patient and can be used to develop and robustly test clinical glycaemic control protocols in a broad range of patients. These effective insulin sensitivity profiles are also rich in dynamics, specifically those circadian in nature which can be identified, and used to provide more accurate glycaemic prediction with the potential for safer and more effective control.

1,25-dihydroxyvitamin D3 (Vitamin D) is a potent immunomodulator capable of generating regulatory T cells (Tregs) and contributing to immune tolerance. Additionally, vitamin D has been shown to promote mucosal immunity when used as a vaccine adjuvant. We show here that pretreatment of an area of skin with the synthetic vitamin D analog calcipotriol combined with transcutaneous immunization results in the induction of CD4⁺CD25⁺ Tregs capable of inhibiting the elicitation of a contact hypersensitivity response. We also demonstrate that topical calcipotriol has significant effects on the immune response to subcutaneously injected vaccines, and compare it with another common topical immunosuppressant, the corticosteroid betamethasone-17-valerate (BMV). Functionally, calcipotriol and BMV treatment both result in the suppression of CD8⁺ T cell priming in response to subcutaneous vaccination, despite the topical co-administration of the potent Th1 inducing TLR9 agonist unmethylated CpG DNA. The effects of calcipotriol on the humoral response are subtler as we observe marginally increased production of antigen-specific IgG1 immunoglobulins along with a strong suppression of the IgG2a isotype. This is in contrast to pretreatment with BMV, which instead suppresses the production of IgG1 and IgA antibodies. In the draining lymph nodes of calcipotriol treated animals, we see no change in the percentage of Foxp3⁺ CD4⁺ T cells post-immunization, but show that tolerance is transferable with the adoptive transfer of CD4⁺CD25⁺ cells. Despite a decrease in the percentage of antigen-bearing APCs in the DLN of calcipotriol treated animals, the DCs maintain high expression of co-stimulatory markers and can induce CD4⁺ T cell proliferation ex vivo. Our data indicate that calcipotriol has distinct effects on immune responses to subcutaneous vaccines consistent with its role as an immunomodulator, although the mechanism(s) through which it is acting remain unclear. We believe that further research is warranted into its potential use as part of a treatment modality for allergy and autoimmune disorders.