Osteoporoza związana z ciążą i laktacją

Osteoporoza związana z ciążą i laktacją (PLO, pregnancy and lactation-associated osteoporosis) to rzadko występująca forma osteoporozy premenopauzalnej o zwykle ciężkim przebiegu, niejednoznacznej przyczynie i nieustalonym sposobie leczenia. Manifestuje się jako silny ból kręgosłupa, zaburzenia jego statyki i zmniejszenie wzrostu pod koniec ciąży lub w okresie laktacji, co wynika z niskoenergetycznych złamań trzonów kręgów. Zaprzestanie laktacji i wdrożenie farmakoterapii(witamina D, teryparatyd, bisfosfoniany) skutkuje zwykle ustąpieniem bólu i znaczną poprawą gęstości mineralnej kości. W dalszym przebiegu choroby, kolejne złamania pojawiają się jednak u ponad 20% kobiet. W pracy przedstawiono trudności w diagnostyce i leczeniu osteoporozy powikłanej wieloogniskowymi złamaniami trzonów kręgów piersiowych i lędźwiowych u kobiety z PLO i z przebytą gruźlicą. Leczenie za pomocą teryparatydu i denosumabu przyniosło poprawę, ale nie spowodowało remisji choroby. Forum Reumatol. 2019, tom 5, nr 2: 97–10

Altering an Artificial Gagpolnef Polyprotein and Mode of ENV Co-Administration Affects the Immunogenicity of a Clade C HIV DNA Vaccine

HIV-1 candidate vaccines expressing an artificial polyprotein comprising Gag, Pol and Nef (GPN) and a secreted envelope protein (Env) were shown in recent Phase I/II clinical trials to induce high levels of polyfunctional T cell responses; however, Env-specific responses clearly exceeded those against Gag. Here, we assess the impact of the GPN immunogen design and variations in the formulation and vaccination regimen of a combined GPN/Env DNA vaccine on the T cell responses against the various HIV proteins. Subtle modifications were introduced into the GPN gene to increase Gag expression, modify the expression ratio of Gag to PolNef and support budding of virus-like particles. I.m. administration of the various DNA constructs into BALB/c mice resulted in an up to 10-fold increase in Gag- and Pol-specific IFNγ+ CD8+ T cells compared to GPN. Co-administering Env with Gag or GPN derivatives largely abrogated Gag-specific responses. Alterations in the molar ratio of the DNA vaccines and spatially or temporally separated administration induced more balanced T cell responses. Whereas forced co-expression of Gag and Env from one plasmid induced predominantly Env-specific T cells responses, deletion of the only H-2d T cell epitope in Env allowed increased levels of Gag-specific T cells, suggesting competition at an epitope level. Our data demonstrate that the biochemical properties of an artificial polyprotein clearly influence the levels of antigen-specific T cells, and variations in formulation and schedule can overcome competition for the induction of these responses. These results are guiding the design of ongoing pre-clinical and clinical trials

Satisfaction and discontent of Polish patients with biological therapy of rheumatic diseases : results of a multi-center questionnaire study

Objectives: Biologics are medications widely applied in the management of inflammatory rheumatic diseases. The drugs were found to be effective but their application is associated with some disadvantages. Medication with biologics is relatively expensive, and in Poland, it is carried out in specialized centers. The study was designed to evaluate various aspects of satisfaction and dissatisfaction of Polish patients treated with biologics. Material and methods: An anonymous questionnaire was distributed in 23 Polish rheumatological centers involved in the treatment; 1212 returned questionnaires were used for analysis. Responses were received from 606 patients with rheumatoid arthritis, 427 with ankylosing spondylitis, 117 psoriatic arthritis, and 62 adult patients with juvenile idiopathic arthritis (in whom administration of the drugs had been introduced before they were 18 years old). The investigated group constituted about one-fifth of all rheumatic patients on biologics in Poland. Results: A beneficial or very beneficial influence of the medication on the state of physical health was found mostly in patients with rheumatoid arthritis (51.3 and 30.5%) and ankylosing spondylitis (51.0 and 36.8%). Family life was improved by the treatment especially in patients with ankylosing spondylitis (40.7 and 35.6% beneficial and very beneficial, respectively), sleep quality and sexual life mostly in those with ankylosing spondylitis (beneficial/very beneficial influence 41.5/38.4, and 38.7/23.9, respectively). There was a rather small influence of biological treatment on the financial situation of the patients. In general, satisfaction with the treatment was evaluated as positive or very positive in 88% of all investigated patients. In a significant part of the patients, transportation to the medical center was considered as a disadvantage of the treatment. About one-third of the patients considered laboratory and imaging tests to be done before initiation of the medication as a difficulty, and for about 40% waiting time for qualification for the medication was a significant disadvantage. The route of drug administration was without importance for 4/5 of the patients. Conclusions: Summing up, the results were similar in the patients suffering from various diseases although those with psoriatic arthritis felt the highest satisfaction (possibly due to the positive aesthetic effect), and those with ankylosing spondylitis had significant improvement in sexual life (probably due to younger age). Relatively low satisfaction was found in patients with juvenile idiopathic arthritis. There was a small influence of medication on financial status of the patients. Application of biologics has few disadvantages and most of them are associated with the organization of health services (waiting time for the tests, transportation to the medical centers)

Pheochromocytoma in 8-year observation at a single endocrinological center in Wroclaw

Wstęp: Guz chromochłonny występuje rzadko, powoduje zwykle nadciśnienie tętnicze i różnorodne, zmienne objawy kliniczne, co często utrudnia wczesne rozpoznanie i leczenie. Celem niniejszej pracy było przedstawienie danych klinicznych, efektywności diagnostyki i leczenia chorych z pheochromocytoma w ośrodku wrocławskim w okresie 8 lat. Materiał i metody: Wśród 37 chorych z pheochromocytoma leczonych w latach 2000-2007 w Klinice Endokrynologii, Diabetologii i Leczenia Izotopami Akademii Medycznej we Wrocławiu były 23 kobiety (23-75 lat) oraz 14 mężczyzn (17-74 lat). Zbadano częstość występowania poszczególnych objawów klinicznych, przydatność zastosowanych metod diagnostycznych i efekty leczenia. Wyniki: Czas trwania choroby do momentu rozpoznania wynosił od 2 miesięcy do 16 lat. Najczęstsze objawy to: nadciśnienie tętnicze napadowe lub stałe, tachykardia, bóle głowy, wzmożona potliwość, niepokój. Najczulszą laboratoryjną metodą diagnostyczną był pomiar stężenia metoksypochodnych katecholamin w moczu dobowym. Tomografia komputerowa u wszystkich chorych wykazała obecność guza nadnercza, częściej prawego; w 1 przypadku guz był umiejscowiony w ścianie pęcherza moczowego. Po operacji nadciśnienie tętnicze ustąpiło u 59% pacjentów, obniżyło się u 26,8%, a u 13,9% nie obserwowano poprawy. U 2 chorych guz był złośliwy, 1 kobieta zmarła po zabiegu. U 8 stwierdzono zespół MEN 2A. Wnioski: Rozpoznania pheochromocytoma zwykle dokonuje się po długim czasie trwania choroby. Najbardziej typowym objawem jest nadciśnienie tętnicze napadowe, które występuje jedynie u około 40%, inne objawy są niespecyficzne. Najbardziej przydatne diagnostycznie jest stwierdzenie podwyższonego wydalania metoksykatecholamin w moczu dobowym. Z badań obrazowych najbardziej efektywna jest tomografia komputerowa. Chorzy z pheochromocytoma powinni być rutynowo diagnozowani w kierunku współistnienia innych endokrynopatii, a szczególnie raka rdzeniastego i pierwotnej nadczynności przytarczyc - składowych zespołu MEN 2A.Introduction: Pheochromocytoma is rare tumor with a highly variable clinical presentation. This report provides clinical picture, efficiency of diagnostics and treatment of pheochromocytoma in 8-years in the endocrinological center in Wroclaw. Material and methods: The records of 37 patients with pheochromocytoma were identified, who were treated in 2000-2007 in the Department of Endocrinology, Diabetology and Isotope Treatment in Wroclaw. There were 23 women (age 23-75 year) and 14 men (age 17-74). We studied frequency of clinical signs, usefulness of diagnostic methods and efficacy of treatment. Results: The duration of the clinical history ranged from 2 months to 16 years. The most frequent symptoms were: hypertension paroxysmal and constant, palpitations, headache, sweating and anxiety. The most sensitive diagnostic method was increased concentration of urinary metanephrine in 24-hour urine. Computed tomography was the most widely used method for tumor localization. Adrenal pheochromocytoma was detecting by CT in all patients, predominated in right adrenal, in 1 case in urinary bladder. Surgery caused remission of hypertension in 59%, improvement in 26.8%, and no changes in 13.9% of patients. Malignancy was reported in 2 cases, 1 woman died after surgery. MEN 2A occur in 21.6%. Conclusions: The diagnosis of pheochromocytma is usually made after long duration of the disease. The study confirms that clinical presentation of pheochromocytoma is variable and nonspecific, this finding makes the diagnosis very difficult. The most typical symptom is paroxysmal hypertension, which is present only in 40%, other symptoms are nonspecific. The measurement of 24-hour urinary metanephrines was the best indicator. CT was almost always successful in localizing the tumor. Patients with pheochromocytoma should be consider for other endocrine diseases especially medullary carcinoma, primary hyperparathyroidism and other component of MEN 2A

Associations between depressive symptoms and disease progression in older patients with chronic kidney disease: results of the EQUAL study

Background Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with earlier phases of chronic kidney disease (CKD). We studied associations between baseline depressive symptoms and clinical outcomes in older patients with advanced CKD and examined whether these associations differed depending on sex. Methods CKD patients (>= 65 years; estimated glomerular filtration rate <= 20 mL/min/1.73 m(2)) were included from a European multicentre prospective cohort between 2012 and 2019. Depressive symptoms were measured by the five-item Mental Health Inventory (cut-off <= 70; 0-100 scale). Cox proportional hazard analysis was used to study associations between depressive symptoms and time to dialysis initiation, all-cause mortality and these outcomes combined. A joint model was used to study the association between depressive symptoms and kidney function over time. Analyses were adjusted for potential baseline confounders. Results Overall kidney function decline in 1326 patients was -0.12 mL/min/1.73 m(2)/month. A total of 515 patients showed depressive symptoms. No significant association was found between depressive symptoms and kidney function over time (P = 0.08). Unlike women, men with depressive symptoms had an increased mortality rate compared with those without symptoms [adjusted hazard ratio 1.41 (95% confidence interval 1.03-1.93)]. Depressive symptoms were not significantly associated with a higher hazard of dialysis initiation, or with the combined outcome (i.e. dialysis initiation and all-cause mortality). Conclusions There was no significant association between depressive symptoms at baseline and decline in kidney function over time in older patients with advanced CKD. Depressive symptoms at baseline were associated with a higher mortality rate in men

Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Publisher Copyright: © 2019, The Author(s).Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.Peer reviewe

Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria

Effects of Primary Processing and Pre-Salting of Baltic Herring on Contribution of Digestive Proteases in Marinating Process

The low-technological quality of herring caught during the feeding season makes it impossible to achieve full ripeness of the meat in marinades. One solution may be to assist ripening using herring digestive tract proteases. Therefore, whole herring, headed herring and fillets were marinated for 2–14 days using the German (direct) and Danish (pre-salted) methods. The results showed that the mass of marinades from fillets was lower than from herring with intestines and correlated strongly with salt concentration in the Danish method, in contrast to the German method. Marinades from whole and headed herring had significantly higher trypsin, chymotrypsin, carboxypeptidase-A and cathepsin activities than marinated fillets. The herring marinated with viscera had 2–3 times higher non-protein nitrogen, peptide and amino acid fractions, as well as ripened 3 days faster than the marinated fillets. After 2 weeks of marinating, the fillets did not achieve full ripeness of the meat, unlike marinades made from whole and headed herring. The pre-salting stage in the Danish method significantly reduced cathepsin D activity by the tenth day of marinating, which was compensated by digestive proteases only in the case of whole or headed herring. The digestive proteases activity in the fillets was too low to achieve the same effect. Sensory evaluation of texture and hardness-TPA correlated strongly with several proteases in whole herring marinades, in contrast to a weak correlation with only one protease when marinating fillets. Marinating with intestines makes it possible to produce marinades faster, more efficiently and with higher sensory quality from herring of low-technological quality