Adolescents with Type 1 diabetes mellitus experience psychosensorial symptoms during hypoglycaemia

AimTo describe mood and psychosensorial symptoms of hypoglycaemia in adolescents with Type 1 diabetes mellitus in two countries with different cultures, Turkey and the USA.MethodsWe developed a 68-item questionnaire assessing physical, behavioural, mood and psychosensorial symptom frequency and ratings [‘good’, ‘bad’, or ‘both’ (sometimes good, sometimes bad)]. Adolescents with Type 1 diabetes were recruited from paediatric diabetes clinics at the University of North Carolina at Chapel Hill in the USA and Kocaeli University in Turkey. The percentages of participants at each clinic who endorsed individual symptoms, symptom categories and symptom ratings were calculated and compared.ResultsCronbach’s α values were > 0.7 for each real symptom category. No symptom items were excluded from the questionnaire analysis based on item-total correlation results which were all > 0.2. Data were collected from 132 participants (69 from University of North Carolina, 63 from Kocaeli University, 54% male). The mean (sd) age of the participants was 14.9 (1.9) years, HbA1c level was 8.7 (1.8) % and duration of Type 1 diabetes was 5.8 (3.7) years. On average, each physical symptom was experienced by 65.2% of participants, each behavioural symptom by 46.5%, each mood symptom by 42.8%, and each psychosensorial symptom by 48.9%. On average, each physical, behavioral, mood and psychosensorial symptom was rated as ‘good’ or ‘both’ by 23.0, 29.1, 36.9 and 37.2% of participants, respectively. There were no symptom differences between the groups in each country.ConclusionsIn addition to the classic physical symptoms experienced during hypoglycaemia, adolescents with Type 1 diabetes report psychosensorial, mood and behavioral symptoms, and some describe them as positive experiences. Symptom experiences were similar in these two countries with different cultures

HLA-A2–Matched Peripheral Blood Mononuclear Cells From Type 1 Diabetic Patients, but Not Nondiabetic Donors, Transfer Insulitis to NOD-scid/γcnull/HLA-A2 Transgenic Mice Concurrent With the Expansion of Islet-Specific CD8+ T cells

OBJECTIVE: Type 1 diabetes is an autoimmune disease characterized by the destruction of insulin-producing beta-cells. NOD mice provide a useful tool for understanding disease pathogenesis and progression. Although much has been learned from studies with NOD mice, increased understanding of human type 1 diabetes can be gained by evaluating the pathogenic potential of human diabetogenic effector cells in vivo. Therefore, our objective in this study was to develop a small-animal model using human effector cells to study type 1 diabetes. RESEARCH DESIGN AND METHODS: We adoptively transferred HLA-A2-matched peripheral blood mononuclear cells (PBMCs) from type 1 diabetic patients and nondiabetic control subjects into transgenic NOD-scid/gammac(null)/HLA-A*0201 (NOD-scid/gammac(null)/A2) mice. At various times after adoptive transfer, we determined the ability of these mice to support the survival and proliferation of the human lymphoid cells. Human lymphocytes were isolated and assessed from the blood, spleen, pancreatic lymph node and islets of NOD-scid/gammac(null)/A2 mice after transfer. RESULTS: Human T and B cells proliferate and survive for at least 6 weeks and were recovered from the blood, spleen, draining pancreatic lymph node, and most importantly, islets of NOD-scid/gammac(null)/A2 mice. Lymphocytes from type 1 diabetic patients preferentially infiltrate the islets of NOD-scid/gammac(null)/A2 mice. In contrast, PBMCs from nondiabetic HLA-A2-matched donors showed significantly less islet infiltration. Moreover, in mice that received PBMCs from type 1 diabetic patients, we identified epitope-specific CD8(+) T cells among the islet infiltrates. CONCLUSIONS: We show that insulitis is transferred to NOD-scid/gammac(null)/A2 mice that received HLA-A2-matched PBMCs from type 1 diabetic patients. In addition, many of the infiltrating CD8(+) T cells are epitope-specific and produce interferon-gamma after in vitro peptide stimulation. This indicates that NOD-scid/gammac(null)/A2 mice transferred with HLA-A2-matched PBMCs from type 1 diabetic patients may serve as a useful tool for studying epitope-specific T-cell-mediated responses in patients with type 1 diabetes

Impact of pharmaceutical promotion on prescribing decisions of general practitioners in Eastern Turkey

<p>Abstract</p> <p>Background</p> <p>Commercial sources of information are known to have greater influence than scientific sources on general practitioners' (GPs) prescribing behavior in under developed and developing countries. The study aimed to determine the self-reported impact of pharmaceutical promotion on the decision-making process of prescription of GPs in Eastern Turkey.</p> <p>Methods</p> <p>A cross-sectional, exploratory survey was performed among 152 GPs working in the primary health centers and hospitals in Erzurum province of Eastern Turkey in 2006. A self-administered structured questionnaire was used. The questionnaire included questions regarding sociodemographics, number of patients per day, time per patient, frequency of sales representative visits to GPs, participation of GPs in training courses on prescribing (in-service training, drug companies), factors affecting prescribing decision, reference sources concerning prescribing and self-reported and self-rated effect of the activities of sales representatives on GPs prescribing decisions.</p> <p>Results</p> <p>Of 152 subjects, 53.3% were male and 65.8% were working at primary health care centers, respectively. Mean patient per day was 58.3 ± 28.8 patients per GP. For majority of the GPs (73.7%), the most frequent resource used in case of any problems in prescribing process was drug guides of pharmaceutical companies. According to self-report of the GPs, their prescribing decisions were affected by participation in any training activity of drug companies, frequent visits by sales representatives, high number of patient examinations per day and low year of practice (p < 0.05 for all).</p> <p>Conclusion</p> <p>The results of this study suggest that for the majority of the GPs, primary reference sources concerning prescribing was commercial information provided by sales representatives of pharmaceutical companies, which were reported to be highly influential on their decision-making process of prescribing by GPs. Since this study was based on self-report, the influence reported by the GPs may have been underestimated.</p

HLA-A2-Matched Peripheral Blood Mononuclear Cells From Type 1 Diabetic Patients, but Not Nondiabetic Donors, Transfer Insulitis to NOD-scid/ cnull/HLA-A2 Transgenic Mice Concurrent With the Expansion of Islet-Specific CD8+ T cells

OBJECTIVEType 1 diabetes is an autoimmune disease characterized by the destruction of insulin-producing β-cells. NOD mice provide a useful tool for understanding disease pathogenesis and progression. Although much has been learned from studies with NOD mice, increased understanding of human type 1 diabetes can be gained by evaluating the pathogenic potential of human diabetogenic effector cells in vivo. Therefore, our objective in this study was to develop a small-animal model using human effector cells to study type 1 diabetes.RESEARCH DESIGN AND METHODSWe adoptively transferred HLA-A2–matched peripheral blood mononuclear cells (PBMCs) from type 1 diabetic patients and nondiabetic control subjects into transgenic NOD-scid/γcnull/HLA-A*0201 (NOD-scid/γcnull/A2) mice. At various times after adoptive transfer, we determined the ability of these mice to support the survival and proliferation of the human lymphoid cells. Human lymphocytes were isolated and assessed from the blood, spleen, pancreatic lymph node and islets of NOD-scid/γcnull/A2 mice after transfer.RESULTSHuman T and B cells proliferate and survive for at least 6 weeks and were recovered from the blood, spleen, draining pancreatic lymph node, and most importantly, islets of NOD-scid/γcnull/A2 mice. Lymphocytes from type 1 diabetic patients preferentially infiltrate the islets of NOD-scid/γcnull/A2 mice. In contrast, PBMCs from nondiabetic HLA-A2–matched donors showed significantly less islet infiltration. Moreover, in mice that received PBMCs from type 1 diabetic patients, we identified epitope-specific CD8+ T cells among the islet infiltrates.CONCLUSIONSWe show that insulitis is transferred to NOD-scid/γcnull/A2 mice that received HLA-A2–matched PBMCs from type 1 diabetic patients. In addition, many of the infiltrating CD8+ T cells are epitope-specific and produce interferon-γ after in vitro peptide stimulation. This indicates that NOD-scid/γcnull/A2 mice transferred with HLA-A2–matched PBMCs from type 1 diabetic patients may serve as a useful tool for studying epitope-specific T-cell–mediated responses in patients with type 1 diabetes

Perforin, granzyme B, and FasL expression by peripheral blood T lymphocytes in emphysema

<p>Abstract</p> <p>Background</p> <p>It is generally accepted that emphysematous lungs are characterized by an increase in the numbers of neutrophils, macrophages, and CD8⁺T lymphocytes, the lasts having increased cytotoxic activity. Because systemic inflammation is also a component of emphysema, we hypothesize that peripheral CD8⁺T lymphocytes of emphysematous smokers who show evidence of systemic inflammation will have higher expression of cytotoxic molecules.</p> <p>Methods</p> <p>We assessed parameters of systemic inflammation in normal individuals (smokers or non-smokers) and in emphysematous subjects with an active smoking history by measuring serum interleukine-6, C-reactive protein, and tumor necrosis factor. Expression of perforin, granzyme B, and FasL protein by CD8⁺T lymphocytes, CD4⁺T lymphocytes, and natural killer cells were assessed by flow cytometry while perforin, granzyme B, and FasL mRNA expression were measured on purified systemic CD8⁺T lymphocytes by real-time PCR.</p> <p>Results</p> <p>Emphysematous smokers had higher levels of serum interleukine-6 than normal subjects. Even with the presence of systemic inflammation in emphysematous smokers, the percentage of peripheral CD8⁺T lymphocytes, CD4⁺T lymphocytes, and NK cells expressing perforin and granzyme B protein was not different between the three groups.</p> <p>Conclusion</p> <p>Despite evidence of systemic inflammation, peripheral T lymphocytes of emphysematous smokers did not show higher levels of cytotoxic markers, suggesting that increase of activated T lymphocytes in the emphysematous lung may be due to either activation in the lung or specific peripheral recruitment.</p

Are skin disorders related to work strain in hospital workers? A cross-sectional study

To evaluate whether occupational stress factors (high demands, low control, low social support, strain, and iso-strain) are associated with skin disorders in hospital workers and whether psychological problems, such as anxiety and depression, act as potential mechanisms through which occupational stress factors are associated with skin disorders

Synergistic Effect of Hyaluronate Fragments in Retinaldehyde-Induced Skin Hyperplasia Which Is a Cd44-Dependent Phenomenon

BACKGROUND: CD44 is a polymorphic proteoglycan and functions as the principal cell-surface receptor for hyaluronate (HA). Heparin-binding epidermal growth factor (HB-EGF) activation of keratinocyte erbB receptors has been proposed to mediate retinoid-induced epidermal hyperplasia. We have recently shown that intermediate size HA fragments (HAFi) reverse skin atrophy by a CD44-dependent mechanism. METHODOLOGY AND PRINCIPAL FINDINGS: Treatment of primary mouse keratinocyte cultures with retinaldehyde (RAL) resulted in the most significant increase in keratinocyte proliferation when compared with other retinoids, retinoic acid, retinol or retinoyl palmitate. RAL and HAFi showed a more significant increase in keratinocyte proliferation than RAL or HAFi alone. No proliferation with RAL was observed in CD44-/- keratinocytes. HA synthesis inhibitor, 4-methylumbelliferone inhibited the proliferative effect of RAL. HB-EGF, erbB1, and tissue inhibitor of MMP-3 blocking antibodies abrogated the RAL- or RAL- and HAFi-induced keratinocyte proliferation. Topical application of RAL or RAL and HAFi for 3 days caused a significant epidermal hyperplasia in the back skin of wild-type mice but not in CD44-/- mice. Topical RAL and HAFi increased epidermal CD44 expression, and the epidermal and dermal HA. RAL induced the expression of active HB-EGF and erbB1. However, treatment with RAL and HAFi showed a more significant increase in pro-HB-EGF when compared to RAL or HAFi treatments alone. We then topically applied RAL and HAFi twice a day to the forearm skin of elderly dermatoporosis patients. After 1 month of treatment, we observed a significant clinical improvement. CONCLUSIONS AND SIGNIFICANCE: Our results indicate that (i) RAL-induced in vitro and in vivo keratinocyte proliferation is a CD44-dependent phenomenon and requires the presence of HA, HB-EGF, erbB1 and MMPs, (ii) RAL and HAFi show a synergy in vitro and in vivo in mouse skin, and (iii) the combination of RAL and HAFi seems to have an important therapeutic effect in dermatoporosis

Plasma leptin and insulin-like growth factor I levels during acute exacerbations of chronic obstructive pulmonary disease

<p>Abstract</p> <p>Background</p> <p>Recent studies have provided evidence for a link between leptin and tumor necrosis factor-alpha (TNF-α). Insulin-like growth factor I (IGF-I) mediates the metabolic effects of growth hormone (GH). The GH axis is believed to be suppressed in chronic obstructive pulmonary disease (COPD). The aim of this study is to find out whether acute exacerbations of COPD are followed by changes in plasma leptin and insulin-like growth factor I (IGF-I) levels and furthermore, whether these changes are related to systemic inflammation.</p> <p>Methods</p> <p>We measured serum leptin, IGF-I, TNF-α, interleukin 1β (IL-1β), interleukin 6 (IL-6) and interleukin 8 (IL-8) levels in 52 COPD patients with acute exacerbation on admission to hospital (Day 1) and two weeks later (Day 15). 25 healthy age-matched subjects served as controls. COPD patients were also divided into two subgroups (29 with chronic bronchitis and 23 with emphysema). Serum leptin and IGF-I were measured by radioimmunoassay and TNF-α, IL-1β, IL-6 and IL-8 were measured by ELISA.</p> <p>Results</p> <p>Serum leptin levels were significantly higher and serum IGF-I levels significantly lower in COPD patients on Day 1 than in healthy controls (p < 0.001). A positive correlation was observed between leptin and TNF-α on Day 1 (r = 0.620, p < 0.001). Emphysematous patients had significantly lower IGF-I levels compared to those with chronic bronchitis both on Day 1 and Day 15 (p = 0.003 and p < 0.001 respectively).</p> <p>Conclusion</p> <p>Inappropriately increased circulating leptin levels along with decreased IGF-I levels occured during acute exacerbations of COPD. Compared to chronic bronchitis, patients with emphysema had lower circulating IGF-I levels both at the onset of the exacerbation and two weeks later.</p