A case of 17-beta-hydroxysteroid dehydrogenase deficiency type 3 in adult endocrinologist practice

17β-Hydroxysteroid dehydrogenase 3 deficiency (17HSD3) is a rare autosomal recessive cause of 46, XY disorders of sex development resulting from HSD17B3 gene mutations, in which conversion of androstenedione to testosterone is impared. The clinical signs of 17HSD3 deficiency depend on the residual activity of the enzyme. The diagnosis of 17HSD3 deficiency is based on reduced testosterone/androstenedione ratio (T/AD < 0.8). Patients are usually assigned at birth and raise as female. If the diagnosis is made before puberty, gonadectomy is recommended, taking into account the risk of masculinization during the puberty and estrogen therapy initiation in this period. If the diagnosis of 17HSD3 deficiency is established during puberty, when virilization manifests, the therapeutic strategy is based on the results of comprehensive psychological testing and gender identity of a patient. In patients with more pronounced masculinization or diagnosis established shortly after birth, who are assigned at birth and raise as male, testosterone therapy is used to achieve a male phenotype. The 17HSD3 deficiency and virilization often result in a change of gender identity during puberty. The article presents a clinical case of 17-βhydroxysteroid dehydrogenase type 3 deficiency with late diagnosis due to parental will. The diagnostic approaches and management of the disease are also described

Transforming growth factor β1 (TGF-β1) in patients with endocrine ophthalmopathy and Graves’ disease: A predictor of treatment efficiency

Current therapeutic approaches to the treatment of endocrine ophthalmopathy (EOP) are based on nonspecific immunosuppression with glucocorticosteroids (GCs) and radiation therapy of the eye orbits. However, some patients exhibit resistance to the treatment. In a previous study, we have detected high levels of soluble cytokine receptors: sTNFα-R1, sTNFα-R2, sIL-2R, and the TGF-β1 cytokine in euthyroid patients with long-lasting non-treated EOP and Graves’ disease (GD). TGF-β1 level was significantly higher in the patients with EOP compared to healthy individuals, and increased with prolonged EOP duration, thus suggesting activation of the factors regulating immune system which promote suppression of the autoimmune process. The aim of this work was to study the dynamics of TGF-β1 and cytokine receptors: sTNFα-R1, sTNFα-R2, sIL-2R in the course of immunosuppressive therapy with high doses of GCs, as possible predictors of treatment efficacy. The study included 49 patients (98 eye orbits) with GD of euthyroid state and subclinical thyrotoxicosis, and the persons with EOP in active phase, who had not previously treatment for EOP. Concentrations of TGF-β1 cytokine, sTNFα-RI and sTNFα-R2, sIL-2R, antibodies to the thyroid-stimulating hormone receptor (rTSH), free fractions of thyroxine (fT4) and triiodothyronine (fT3), TSH in blood serum were determined in blood serum. Ultrasound examination of the thyroid gland (ultrasound of the thyroid gland), multi-layer computed tomography (MSCT)/magnetic resonance imaging (MRI) of the orbits were also performed. The patients were administered immunosuppressive therapy with high doses of HCs (methylprednisolone) in the course of pulse therapy, at a standard dosage of 4500-8000 mg, taking into account the severity and activity of the EOP clinical manifestations. The examination was carried out 3, 6, 12 months after starting the treatment. 3 and 6 months after the GC administration, more than 30% of patients remained resistant to treatment. The levels of TGF-β1 did not change significantly in the patients with positive EOP dynamics. In the patients resistant to GC treatment, the level of TGF-β1 was significantly decreased compared with patients who showed positive clinical dynamics. The level of sNFR1 and sNFaR2 did not change significantly. There were no significant differences in the levels of antibodies to rTSH, thyroid hormones in the patients resistant to GC treatment and with positive dynamics.Immunosuppressive therapy with high-dose of methylprednisolone in pulse therapy regimen showed high efficacy and good tolerability, while some patients remain resistant to treatment. Lower levels of TGF-β1 cytokine at initial time and during the treatment allow usage of TGF-β1 levels as a biomarker of the activity of the process, treatment efficiency, and prognosis of the disease. Activation of TGF-β1, a fibroblast growth factor, may contribute to the development of fibrosis, strabismus, and diplopia

Investigation of initiation of gigantic jets connecting thunderclouds to the ionosphere

The initiation of giant electrical discharges called as "gigantic jets" connecting thunderclouds to the ionosphere is investigated by numerical simulation method in this paper. Using similarity relations, the triggering conditions of streamer formation in laboratory situations are extended to form a criterion of initiation of gigantic jets. The energy source causing a gigantic jet is considered due to the quasi-electrostatic field generated by thunderclouds. The electron dynamics from ionization threshold to streamer initiation are simulated by the Monte Carlo technique. It is found that gigantic jets are initiated at a height of ~18-24 km. This is in agreement with the observations. The method presented in this paper could be also applied to the analysis of the initiation of other discharges such as blue jets and red sprites.Comment: 12th International Congress on Plasma Physics, 25-29 October 2004, Nice (France

Apokamps produced by repetitive discharges in air

New experimental and computational data on apokamps produced by repetitive discharges in air, including a detailed description of the research techniques used, are presented. It has been shown that plasma bullets–streamers in apokamps at low frequencies could start not only from the bright offshoot but also directly from the discharge channel. The experimental and computational data demonstrate that the visual color of apokamp changes from blue to red as the intensity ratio of the second to the first positive nitrogen system decreases with the decreasing pressure

Determining the Amount of Phenylpropanoids in Belowground Organs of Purple Coneflower (Echinacea purpurea (L.) Moench., Asteraceae)

От эхинацеи пурпурной получают виды лекарственного растительного сырья: траву свежую и высушенную, корневища с корнями. В них содержится сумма фенилпропаноидов (ранее «оксикоричные кислоты», «гидроксикоричные кислоты») и их производные, обеспечивающие иммуностимулирующий эффект препаратов, основным из которых является настойка. Накопление суммы фенилпропаноидов в корневищах с корнями эхинацеи наименее изучено. Цель – изучение влияния сроков и кратности удаления надземной части на содержание суммы фенилпропаноидов в корневищах с корнями эхинацеи, полученных от растений разных возрастов при культивировании, а также определение содержания изучаемых веществ в настойке при разной степени измельчения сырья. Исследованы корневища с корнями эхинацеи пурпурной, заготовленные в Москве в 2008–2010 гг. в фазу окончания вегетации растений 2-го, 3-го, 4-го, 5-го, 7-го гг. развития. Побеги скашивали в фазы стеблевания (однократно и многократно в течение вегетации), бутонизации, цветения. Контроль – получение сырья без удаления надземной части. В 2008–2009 гг. наибольшее накопление суммы фенилпропаноидов в подземных органах наблюдали при многократном и однократном скашивании побегов в период стеблевания, независимо от возраста растений. Удаление побегов в фазах бутонизации и цветения привело к значительному снижению содержания суммы фенилпропаноидов. В июле-августе 2010 г. в регионе была засуха. Наименьшее содержание изучаемых веществ в сырье отмечено при многократном удалении побегов. В лучшем положении оказалось сырье растений, у которых надземную массу срезали однократно в фазу стеблевания. При сравнении растений разных возрастов установлено, что в сырье растений 2–4 гг. вегетации накопление веществ, независимо от срока удаления надземной части и года проведения опыта, достоверно выше, чем в сырье от растений старших возрастов. Рекомендовано дополнить «Агрорекомендацию по возделыванию эхинацеи пурпурной» при выращивании для получения корневищ с корнями агроприемом многократного скашивания надземной части в фенологической фазе стеблевания. Влияние размера частиц измельченного сырья (от 0,25 мм до 1,0 мм) на содержание биологически активных веществ в настойке не наблюдалосьEchinacea purpurea (L.) Moench plants serve as a source of medicinal raw materials: fresh and dried aboveground parts and rhizomes with roots (Rhizomata cum radicibus). They contain total phenylpropanoids (formerly “oxycinnamic acids”, “hydroxycinnamic acids”) and their derivatives, which underlie the immunostimulatory effect of the preparations. Tincture is the most common preparation. Accumulation of total phenylpropanoid derivatives in Echinacea rhizomes with roots is the least studied aspect. The purpose of the present work is to study the effect of the timing and frequency of removal of the aboveground part on total phenylpropanoids in Echinacea rhizomes with roots collected from cultivated plants of different ages. Another aim was to determine total phenylpropanoids in the tincture prepared from raw material ground to various degrees. Echinacea purpurea rhizomes with roots harvested in Moscow in 2008–2010, at the end of the growing period of plants aged 2, 3, 4, 5, and 7 years, were studied. The shoots were cut down during the stem formation (by single and repeated mowing during the growing period), budding, and flowering stages. The intact raw material was used to provide control samples. In 2008–2009, the highest accumulation of phenylpropanoid derivatives in rhizomes with roots was observed in groups with both repeated and single shoot removals performed during the shoot development stage at all plant ages. The shoot removals during the budding and flowering stages resulted in a significant reduction in phenylpropanoids. During the regional drought in July and August 2010, the raw material samples in the group with repeated shoot removals demonstrated the lowest accumulation of phenylpropanoids. The samples in the group with single shoot removal during the shoot development stage showed greater phenylpropanoid accumulation compared with the repeated mowing group. The content of phenylpropanoids in raw material from 2–4-year-old plants, regardless of the period of shoot removal and the year of the experiment, was significantly higher than in the raw material from older plants. It is recommended to supplement the “Agro-recommendation for the cultivation of Echinacea purpurea” with the agricultural method of repeated mowing of the aboveground part in the phenological phase of shoot development when the plant is grown as a source of rhizomes with roots. No effect of the particle size of the ground raw material (from 0.25 to 1.0 mm) on total phenylpropanoids in the tincture has been reveale

Factors affecting the results of analgesic therapy. Results of the Russian multicentre study of NOTE (NSAID: Open-label Trial of Efficacy)

Non-steroidal anti-inflammatory drugs (NSAIDs) are most popular medications for the treatment of pain in common musculoskeletal diseases such as osteoarthritis (OA) and non-specific low back pain (LBP). However, the factors affecting the effectiveness of these drugs have not been determined fully. Aim: to identify factors affecting the effectiveness of NSAIDs in patients with OA and LBP. Materials and methods. An observational study was conducted to evaluate the effectiveness of a 2-week course of NSAIDs in OA and LBP in real clinical practice. The study group consisted of 3604 patients with OA and LBP (60.6% women and 39.4% men, mean age 55.0±13.4 years). According to the study design, aceclofenac (Airtal) and other NSAIDs used in the ratio 1:1. The main criterion of effectiveness was the frequency of complete pain relief after 2 weeks of therapy. In addition, the decrease of pain and general health were determined on a 10-point numerical rating scale (NRS). We compared the frequency of complete pain relief in patients who had and did not have the studied factors. The value of the studied factors was determined using OR (95% CI). Results and discussion. Most patients received aceclofenac (54.9%), as well as diclofenac (2.0%), ketoprofen (1.9%), lornoxicam (2.2%), meloxicam (13.7%), naproxen (2.1%), nimesulide (5.8%), celecoxib (5.9%), ethicoxib (7.1%) and other NSAIDs (4.4%); 56.2% of patients received muscle relaxants, mainly tolperisone (74.7%), vitamin B (10.4%), and proton pump inhibitors (42.8%). Complete pain relief was achieved in 54.8% of patients. The pain decrease and general health improvement were (for NRS) 63.9±13.4% and 61.7±14.8%, respectively. The efficacy of aceclofenac was slightly higher than in the whole group: complete pain relief was in 59.9% of patients. Adverse events in aceclofenac use were observed in 2.3% of patients, other NSAIDs-from 2.4 to 14.1%. The frequency of complete pain relief was higher in men: OR 1,239 (95% CI 1.08-1.418; p=0.002), who had the first episode of pain - OR 3.341 (95% CI 2.873-3.875; p=0.000), a good" response " to NSAIDs in history - OR 1.656 (95% CI 1.385-1.980; p=0.000) and received NSAIDs in combination with muscle relaxants - OR 1.218 (95% CI 1.067-1.390; p=0.004). The effect of therapy is lower in patients 65 years and older-OR 0,378 (95% CI 0.324-0.442; p=0,000), with body mass index >30 kg/m² - OR 0.619 (95% CI 0.529-0.723; p=0.000), with severe pain (≥7 points NRS) - OR 0.662 (95% CI 0.580-0.756; p=0.002), with pain at rest, - OR 0.515 (95% CI 0.450-0,589; p=0.000), pain at night - OR 0.581 (95% CI 0.501-0.672; p=0.000) and the presence of stiffness - OR 0.501 (95% CI 0.438-0,573; p=0.000). Treatment results are significantly worse in the cases of combination of LBP and joint pain, as well as pain in the trochanter major and pes anserinus area (