Celiakia w chorobach endokrynologicznych pochodzenia autoimmunologicznego

Abstract Coeliac disease (CD, sometimes called gluten-sensitive enteropathy or nontropical sprue) is an inflammatory disorder of the small intestine of autoimmune origin. It occurs in genetically predisposed people and is induced by a gluten protein, which is a component of wheat. The prevalence of histologically confirmed CD is estimated in screening studies of adults in the United States and Europe to be between 0.2% and 1.0%. The results of previous studies have indicated that the prevalence of CD is increased in patients with other autoimmune disorders such as: autoimmune thyroid diseases, type 1 diabetes mellitus, and Addison’s disease. A coincidence of the above diseases constitutes autoimmune polyglandular syndrome (APS). The high prevalence of CD in APS is probably due to the common genetic predisposition to the coexistent autoimmune diseases. The majority of adult patients have the atypical or silent type of the disease. This is the main reason why CD so often goes undiagnosed or the diagnosis is delayed. CD, if undiagnosed and untreated, is associated with many medical disorders including haematological (anaemia), metabolical (osteopenia/osteoporosis), obstetric-gynaecological (infertility, spontaneous abortions, late puberty, early menopause), neurological (migraine, ataxia, epilepsy) as well as with an increased risk of malignancy, especially: enteropathy-associated T-cell lymphoma, small intestine adenocarcinoma, and oesophageal and oropharyngeal carcinomas. Early introduction of a gluten-free diet and lifelong adherence to this treatment decreases the risk of these complications.Celiakia (inaczej: glutenozależna choroba trzewna, enteropatia glutenowrażliwa, sprue nietropikalna) jest enteropatią zapalną jelita cienkiego o podłożu autoimmunologicznym, spowodowaną trwałą nietolerancją glutenu zawartego w zbożach, występującą u osób z predyspozycją genetyczną. Częstość potwierdzonej histopatologicznie celiakii w ogólnej populacji dorosłych, według wyników badań przesiewowych przeprowadzonych w Europie oraz Stanach Zjednoczonych, wynosi 0,2–1,0%. Wyniki dotychczasowych badań sugerują, że ryzyko zachorowania na celiakię jest kilkakrotnie większe u pacjentów z innymi chorobami autoimmunologicznymi, jak np.: choroby autoimmunologiczne tarczycy (AITD), cukrzyca typu 1 (T1D) czy choroba Addisona. Powyższe choroby wchodzą w skład autoimmunologicznych zespołów niedoczynności wielogruczołowej (APS). Jedną z przyczyn większej częstości występowania celiakii w APS, w porównaniu z ogólną populacją, jest prawdopodobnie wspólna predyspozycja genetyczna. U osób dorosłych zdecydowaną większość przypadków stanowią postacie atypowe i nieme. Wpływa to na opóźnioną i obniżoną wykrywalność choroby. Nierozpoznana i nieleczona celiakia może prowadzić do wielu zaburzeń, w tym m.in.: hematologicznych (niedokrwistość), metabolicznych (osteopenia/osteoporoza), ginekologiczno-położniczych (niepłodność, wzrost częstości samoistnych poronień, opóźnione dojrzewanie i wcześniejsza menopauza) i neurologicznych (migrena, ataksja, padaczka). Nieleczona celiakia zwiększa również ogólne ryzyko zachorowania na złośliwe nowotwory, w tym przede wszystkim na: chłoniaka jelita cienkiego, gruczolakoraka jelita cienkiego, gardła i przełyku. Skuteczne leczenie (dieta bezglutenowa), wprowadzone wcześnie i kontynuowane przez całe życie, zmniejsza ryzyko wystąpienia wymienionych powikłań

Bone metabolism and vitamin D status in patients with multiple sclerosis

Background Vitamin D (VD), an important factor for bone health immobilization and immune regulation, has been shown to have low serum concentration in multiple sclerosis (MS) patients. Those patients have also multiple fracture risk factors, including progressive immobilization and long-term glucocorticoids treatment. The aim of the study was to analyze bone health (osteopenia or osteoporosis prevalence) and VD serum concentration in MS patients as well as the influence of disease activity and treatment on bone health. Materials and methods The study involved 72 MS patients: 52 women and 20 men. Mean age was 40.3±10.5 yrs, mean EDSS (Expanded Disability Status Scale) 3.3±1.9. Bone health was analyzed using standard densitometry in the lumbar spine and femoral neck. Serum levels of VD, calcium, phosphate and parathormone were assessed. We compared two groups of patients with multiple sclerosis: relapsing - remitting MS (RRMS) and progressive relapsing MS (PRMS). Results Densitometry revealed osteopenia in twenty-six (36.1%) patients and osteoporosis in eleven (15.3%), no bone fractures were presented. Sixty-eight MS patients (94.4%) had lower VD serum level if compared to population referential values. Thirteen patients (18.1%) had severe VD deficiency. Densitometry parameter (T-score of the lumbar spine) worsened with EDSS increase (r=−0.43, P=0.001). There was a statistically significant negative correlation between VD concentration and EDSS score (r=−0.31; P=0.009). Conclusions Our study indicates that patients with MS have high incidence of osteopenia and osteoporosis and vitamin D deficiency. Bone health disturbances studied by densitometry are related to the disability caused by MS

IL-33 stimulates expression of the GPR84 (EX33) fatty acid receptor gene and of cytokine and chemokine genes in human adipocytes

Expression of GPCR fatty acid sensor/receptor genes in adipocytes is modulated by inflammatory mediators, particularly IL-1β. In this study we examined whether the IL-1 gene superfamily member, IL-33, also regulates expression of the fatty acid receptor genes in adipocytes. Human fat cells, differentiated from preadipocytes, were incubated with IL-33 at three different dose levels for 3 or 24 h and mRNA measured by qPCR. Treatment with IL-33 induced a dose-dependent increase in GPR84 mRNA at 3 h, the level with the highest dose being 13.7-fold greater than in controls. Stimulation of GPR84 expression was transitory; the mRNA level was not elevated at 24 h. In contrast to GPR84, IL-33 had no effect on GPR120 expression. IL-33 markedly stimulated expression of the IL1B, CCL2, IL6, CXCL2 and CSF3 genes, but there was no effect on ADIPOQ expression. The largest effect was on CSF3, the mRNA level of which increased 183-fold over controls at 3 h with the highest dose of IL-33; there was a parallel increase in the secretion of G-CSF protein into the medium. It is concluded that in human adipocytes IL-33, which is synthesised in adipose tissue, has a strong stimulatory effect on the expression of cytokine and chemokine genes, particularly CSF3, and on the expression of GPR84, a pro-inflammatory fatty acid receptor

Intracerebral haemorrhage after amphetamine use

Krwotok śródmózgowy (ICH) należy do typów udaru o najpoważniejszym rokowaniu. Charakteryzuje się ciężkim przebiegiem klinicznym oraz wysoką śmiertelnością (60%). Do najczęstszych czynników etiologicznych ICH należą nadciśnienie tętnicze oraz obecność malformacji naczyniowej w obrębie ośrodkowego układu nerwowego (OUN). Pierwotny (nieurazowy) ICH może wystąpić również po zażyciu substancji psychoaktywnych, które stanowią istotny czynnik ryzyka krwawienia do OUN, zwłaszcza u osób młodych. W poniższej pracy zaprezentowano przypadek młodej kobiety, u której udar krwotoczny wystąpił po zażyciu amfetaminy. Wykonane badania neuroobrazowe wykluczyły inne przyczyny krwawienia, takie jak malformacja naczyniowa czy guz mózgu. W tym przypadku rokowanie okazało się pomyślne, a stosowane leczenie zachowawcze oraz rehabilitacja ruchowa korzystnie wpłynęły na stan funkcjonalny pacjentki.Intracerebral haemorrhage (ICH) is one of the most devastatingforms of stroke. It is characterized by a severe clinical course and high mortality (60%). The most common etiological risk factors are: hypertension and vascular malformation. Amphetamine-like stimulants abuse can be also considered as a cause of intracranial haemorrhage. Young people seem to be the main group at risk. In this study we present a young female with ICH subsequent to amphetamine intake. The patient underwent brain computed tomography, magnetic resonance imaging and angiography. Basing on performed examinations we excluded vascular malformation and brain tumor. Therefore we suspect that the ICH in our patient may be attributed to the effect of amphetamine alone. In this case the outcome proved to be successful. Medical treatment and physical rehabilitation had positive influence on functional status of patient

Total testosterone to dihydrotestosterone ratio assessed by LC-MS/MS predicts a worse metabolic profile not only in PCOS patients

Objectives: Total testosterone/dihydrotestosterone ratio (TT/DHT) was found to determine metabolic risk in polycystic ovary syndrome (PCOS). The aim of this study was to analyze whether (TT/DHT) may be helpful in predicting metabolic risk not only in PCOS patients but also in healthy women. Material and methods: Total testosterone (TT), dihydrotestosterone (DHT), androstendione and dehydroepiandrosterone sulphate (DHEA-S) were measured by LC-MS/MS in 36 women with PCOS and in 29 age-matched controls without clinical hyperandrogenism. In all participants, anthropometric data, lipids, adipose tissue percent (%fat), HOMA-IR were also assessed. Results: The studied groups were not different in terms of age, BMI, waist circumference, %fat and HOMA-IR. In the patients group, mean TT and androstendione levels were significantly higher as compared to controls (1.4 nmol/L vs. 1.0 nmol/L, P < 0.001) and (6.6 nmol/L vs. 4.9 nmol/L, P < 0.01), respectively. In the patients group, mean TT/DHT ratio was significantly higher compared to controls (3.6 vs. 2.7, P < 0.01) and correlated with BMI (r = 0.37, P < 0.05), waist circumference (r = 0.44, P < 0.01), %fat (r = 0.30, P < 0.05), as well as with insulin levels (r = 0.38, P < 0.05) and HOMA-IR (r = 0.44, P < 0.05). The association between TT/DHT ratio and unfavorable metabolic parameters was also seen in controls. Conclusion: Total testosterone/dihydrotestosterone ratio assessed by LC-MS/MS correlates with a worse metabolic profile not only in PCOS patients, but also in healthy women

Preventive effects of Salvia officinalis leaf extract on insulin resistance and inflammation in a model of high fat diet-induced obesity in mice that responds to rosiglitazone

Background Salvia officinalis (sage) is a native plant to the Mediterranean region and has been used for a long time in traditional medicine for various diseases. We investigated possible anti-diabetic, anti-inflammatory and anti-obesity effects of sage methanol (MetOH) extract in a nutritional mouse model of obesity, inflammation and insulin resistance, as well as its effects on lipolysis and lipogenesis in 3T3-L1 cells. Methods Diet-induced obese (DIO) mice were treated for 5 weeks with sage methanol extract (100 and 400 mg.kg-1/day. bid), or rosiglitazone (3 mg.kg-1/day. bid), as a positive control. Energy expenditure, food intake, body weight, fat mass, liver glycogen and lipid content were evaluated. Blood glucose, and plasma levels of insulin, lipids leptin and pro- and anti-inflammatory cytokines were measured throughout the experiment. The effects of sage MetOH extract on lipolysis and lipogenesis were tested in vitro in 3T3-L1 cells. Results After two weeks of treatment, the lower dose of sage MetOH extract decreased blood glucose and plasma insulin levels during an oral glucose tolerance test (OGTT). An insulin tolerance test (ITT), performed at day 29 confirmed that sage improved insulin sensitivity. Groups treated with low dose sage and rosiglitazone showed very similar effects on OGTT and ITT. Sage also improved HOMA-IR, triglycerides and NEFA. Treatment with the low dose increased the plasma levels of the anti-inflammatory cytokines IL-2, IL-4 and IL-10 and reduced the plasma level of the pro-inflammatory cytokines IL-12, TNF-α, and KC/GRO. The GC analysis revealed the presence of two PPARs agonist in sage MetOH extract. In vitro, the extract reduced in a dose-related manner the accumulation of lipid droplets; however no effect on lipolysis was observed. Conclusions Sage MetOH extract at low dose exhibits similar effects to rosiglitazone. It improves insulin sensitivity, inhibits lipogenesis in adipocytes and reduces inflammation as judged by plasma cytokines. Sage presents an alternative to pharmaceuticals for the treatment of diabetes and associated inflammation

Total testosterone to dihydrotestosterone ratio assessed by LC-MS/MS predicts a worse metabolic profile not only in PCOS patients

Objectives: Total testosterone/dihydrotestosterone ratio (TT/DHT) was found to determine metabolic risk in polycystic ovary syndrome (PCOS). The aim of this study was to analyze whether (TT/DHT) may be helpful in predicting metabolic risk not only in PCOS patients but also in healthy women. Material and methods: Total testosterone (TT), dihydrotestosterone (DHT), androstendione and dehydroepiandrosterone sulphate (DHEA-S) were measured by LC-MS/MS in 36 women with PCOS and in 29 age-matched controls without clinical hyperandrogenism. In all participants, anthropometric data, lipids, adipose tissue percent (%fat), HOMA-IR were also assessed. Results: The studied groups were not different in terms of age, BMI, waist circumference, %fat and HOMA-IR. In the patients group, mean TT and androstendione levels were significantly higher as compared to controls (1.4 nmol/L vs. 1.0 nmol/L, P &lt; 0.001) and (6.6 nmol/L vs. 4.9 nmol/L, P &lt; 0.01), respectively. In the patients group, mean TT/DHT ratio was significantly higher compared to controls (3.6 vs. 2.7, P &lt; 0.01) and correlated with BMI (r = 0.37, P &lt; 0.05), waist circumference (r = 0.44, P &lt; 0.01), %fat (r = 0.30, P &lt; 0.05), as well as with insulin levels (r = 0.38, P &lt; 0.05) and HOMA-IR (r = 0.44, P &lt; 0.05). The association between TT/DHT ratio and unfavorable metabolic parameters was also seen in controls. Conclusion: Total testosterone/dihydrotestosterone ratio assessed by LC-MS/MS correlates with a worse metabolic profile not only in PCOS patients, but also in healthy women

Non-Acidic Free Fatty Acid Receptor 4 Agonists with Antidiabetic Activity

The free fatty acid receptor 4 (FFA4 or GPR120) has appeared as an interesting potential target for the treatment of metabolic disorders. At present, most FFA4 ligands are carboxylic acids that are assumed to mimic the endogenous long-chain fatty acid agonists. Here, we report preliminary structure-activity relationship studies of a previously disclosed nonacidic sulfonamide FFA4 agonist. Mutagenesis studies indicate that the compounds are orthosteric agonists despite the absence of a carboxylate function. The preferred compounds showed full agonist activity on FFA4 and complete selectivity over FFA1, although a significant fraction of these noncarboxylic acids also showed partial antagonistic activity on FFA1. Studies in normal and diet-induced obese (DIO) mice with the preferred compound 34 showed improved glucose tolerance after oral dosing in an oral glucose tolerance test. Chronic dosing of 34 in DIO mice resulted in significantly increased insulin sensitivity and a moderate but significant reduction in bodyweight, effects that were also present in mice lacking FFA1 but absent in mice lacking FFA4

PCR array and protein array studies demonstrate that IL-1β (interleukin-1β) stimulates the expression and secretion of multiple cytokines and chemokines in human adipocytes

The role of IL-1β in regulating the expression and secretion of cytokines and chemokines by human adipocytes was examined. Adipocytes were incubated with human IL-1β for 4 or 24 h. The expression of a panel of 84 cytokine/chemokine genes was probed using PCR arrays. IL-1β stimulated the expression of >30 cytokine/chemokine genes on the arrays; 15 showed >100-fold increases in mRNA at 4 or 24 h including CSF3, CXCL1, CXCL2, CXCL12 and IL8. CSF3 exhibited a 10,000-fold increase in mRNA at 4 h. ADIPOQ was among the genes whose expression was inhibited. Protein arrays were used to examine the secretion of cytokines/chemokines from adipocytes. IL-1β stimulated the secretion of multiple cytokines/chemokines including MCP-1, IL-8, IP-10, MIP-1α and MCP-4. The most responsive was IP-10, which exhibited a 5,000-fold increase in secretion with IL-1β. IL-1β is likely to play a substantial role in stimulating the inflammatory response in human adipocytes in obesity