Long-term outcomes of ruxolitinib therapy in steroid-refractory graft-versus-host disease in children and adults.

Acute and chronic steroid-refractory graft-versus-host disease (srGVHD) is a life-threatening complication of allogeneic stem cell transplantation. There are a number of reports on case series describing efficacy of ruxolitinib in both acute and chronic srGVHD. We conducted a prospective study (NCT02997280) in 75 patients with srGVHD (32 acute, 43 chronic, 41 adults, and 34 children). Patients with chronic GVHD had severe disease in 83% of cases, and acute GVHD patients had grade III-IV disease in 66% of cases. The overall response rate (ORR) was 75% (95% CI 57-89%) in acute GVHD and 81% (95% CI 67-92%) in chronic. Overall survival was 59% (95% CI 49-74%) in acute group and 85% (95% CI 70-93%). The major risk factors for lower survival were grade III-IV gastrointestinal involvement (29% vs 93%, p = 0.0001) in acute form and high disease risk score in chronic (65% vs 90%, p = 0.038). Toxicity was predominantly hematologic with 79% and 44% of grade III-IV neutropenia in acute and chronic groups, respectively. There was no difference between adults and children in terms of ORR (p = 0.31, p = 0.35), survival (p = 0.44, p = 0.12) and toxicity (p > 0.93). The study demonstrated that ruxolitinib is an effective option in acute and chronic srGVHD and can be used both in adults and children.

The role of progestogen supplementation (dydrogesterone) in the prevention of preeclampsia.

Our goal was determine the effects of dydrogesterone supplementation to reduce the incidence of preeclampsia (PE) in early pregnancy (from 6 to 20 weeks of gestation). A total of 406 pregnant women were involved into the study. The Study group enrolled 169 women, supplemented with dydrogesterone at a dose of 30 mg/d 6-20 weeks of gestation compared with the control group (237 subjects) - without dydrogesterone supplementation. The women were randomized by age, race, obstetrics complications, and their somatic history. The use of dydrogesterone in early pregnancy - before 20 weeks of gestation (at a dose of 30 mg/d) with high-risk factors of PE contributed to a statistically significant reduction in the frequency of this complication (13.1% and 71.4%, p < .001). It was seen, that women who took dydrogesterone developed significantly less such disorders like hypertension (3.2% and 71.2%, p < .001), proteinuria (0.0% and 66.18%, p < .001), fetal growth retardation syndrome (2.2% and 21.58%, p < .001), destroy of uteri-placenta velocity (3.2% and 21.58%, p < .001), preterm labor (8.6% and 53.95%, p < .001). Dydrogesterone supplementation in the first and second period of pregnancy (from 6 to 20 weeks of gestation) significantly reduced the incidence of PE in women with higher risk pregnancy.

[Structural and functional changes in the retinal layers in patients with primary glaucoma and possible means of retinoprotection]. / Strukturno-funktsional'nye izmeneniia sloev setchatki pri pervichnoi glaukome i vozmozhnye puti retinoprotektsii.

Glaucoma is one of the most severe forms of ophthalmic pathology which can lead to low vision and blindness. Therapy aimed only at reducing intraocular pressure (IOP) may be insufficient in patients with this disease. PURPOSE: To study the structural and functional changes occurring in the retina and the effect of peptide bioregulator on the state of various retinal layers in patients with primary open-angle glaucoma (POAG). MATERIAL AND METHODS: The study included 62 patients (123 eyes) with POAG. The control group consisted of 25 people (50 eyes) of the same age. After the initial examination, patients of the glaucomatous group were divided into two equal subgroups. Patients of the first subgroup received 10 intramuscular injections of the peptide bioregulator; in the second subgroup, patients did not receive any retinoprotective therapy. The state of the visual analyzer was assessed using spectral optical coherence tomography (SOKT), electrophysiological research methods (ERG, PERG, flicker ERG), photostress test. RESULTS: Patients with POAG were found to have current and developing changes in the thickness and the configuration of various layers of the retina in the macular area as the disease progresses - particularly, in the nerve fiber layer (p=0.02), ganglion cells (p=0.002), inner nuclear layer (p=0.003) and the layer of pigment epithelium (p=0.049). Electrophysiological research methods helped reveal statistically significant changes in the functional parameters reflecting the generation and conduction of nerve impulses in retinal layers in patients with glaucoma. The patients undergoing peptide bioregulator therapy showed statistically significant positive changes in the state of ganglion cells observed as a decrease in the latency of the PERG N-95 wave (p=0.002) and stabilization of the structural indicators of SOCT (RNFL peripapillary zone). CONCLUSION: Patients with POAG exhibit progressive decrease in the thickness of not only the inner, but also the outer layers of the retinal macular area. According to objective structural and functional criteria, retinoprotective therapy leads to stabilization of the glaucomatous process.

[Young and old animals use different strategies for forming an immune response to infectious agents (Pseudomonas aeruginosa и Escherichia coli).]

Features of the immune response to injection of suspension of bacteria (Pseudomonas aeruginosa and Escherichia coli) in young (3 months) and old (20 months) Wistar rats at 3, 5 and 7 days after infection were investigated. The dynamics of the content of circulating immune complexes (CEC), complement C3 fragments, and the activity of oxygen-dependent and oxygen-independent phagocytosis were determined. It was shown that infection was accompanied by a multiple increase in the content of circulating immune complexes in young and, especially, in old animals. It remained at a high level from the 3d to the 7th day of the development of pathology in young animals, while they content decreased to 7 days in old animals. On the background of the development of the infectious process, the content of complement C3 fragments decreased in young animals, and it increased in old animals, in the case of infection with P. aeruginosa and E. coli. The activity of oxygen-dependent and oxygen-independent phagocytosis decreased in different ways in young and old animals on the background of infections, i.e. the ratio of the forms of phagocytosis in old and young animals was different. Old animals were not inferior to the young in terms of the ability of the immune system to respond to the presence of an infectious agent. So they used a different strategy for forming the immune response.

Comparative evaluation of the depth of collagen and hyaluronic acid hydrolysis in vitro by collagenase and hyaluronidase preparations.

The molecular weights of collagen and hyaluronic acid solutions after their incubation with collagenase and hyaluronidase were evaluated by capillary viscosimetry. The results indicate high amylolytic activity of collagenase and the absence of proteolytic activity in hyaluronidase in an in vitro system.

[The levels of nitrites and medium molecular-weight molecules in the blood of neonatal infants with posthypoxic cardiopathy].

A hundred and four neonatal infants underwent clinical and functional studies in early neonatality. The levels of nitrites and medium molecular-weight molecules were determined in cardiologically healthy neonatal infants and children with posthypoxic cardiopathy. The magnitude of increases in biochemical parameters was found to be associated with clinical type of cardiopathy: their level significantly elevates in transient myocardial ischemia, their values achieve the maximum level in neonatal pulmonary hypertension and in the presence of functioning fetal communications.

[Biochemical criteria in diagnosis of some causes of death].

The article presents biochemical indices of blood and tissues obtained at autopsy which can be used for diagnosis of strangulation asphyxia, poisoning with alcohol substitutes, hyperglycemic coma and hepatic insufficiency.

Dynamics of hydration of cicatricial tissue during local therapy with collagenase preparations.

The components of complex dielectric permeability of cicatricial tissue at the frequency of 55 GHz were studied during local therapy of cicatrices with Fermenkol (a complex of collagenolytic proteases). Electrical characteristics of tissues in the microwave range were interpreted in terms of hydration parameters (total content of water in tissues and the ratio of structured and free water). The rightfulness of interpretations is discussed on the basis of the results of measurements of cell suspension models (native blood and its fractions brought to a standard hematocrit). The results attest to a relationship between hydration of the cicatricial tissue and its morphology and function.

Role of sex hormones in cardiovascular resistance to atropine in rats at rest and during stress.

Castration of males and females reduces the sensitivity of cardiac chronotropic function to atropine and potentiates the vascular component in the reaction to atropine in females (during stress) and males (at rest and during stress). Our results show that estrogens and androgens increase the sensitivity of the cardiovascular system to cholinergic influences at rest and during stress.

Prenatal stress alters cardiovascular responses in adult rats.

Environmental factors in early life are clearly established risk factors for cardiovascular disease in later life. Most studies have focused on nutritional programming and analysed basal cardiovascular parameters rather than responses. In the present study we have investigated whether prenatal stress has long-term effects on cardiovascular responses in adult offspring. Female pregnant Sprague-Dawley rats were subjected to stress three times daily from day 15 to day 21 of gestation. Litters from stressed and control females were cross-fostered at birth to control for mothering effects. When the offspring were 6 months old, blood pressure was measured in the conscious rats through implanted catheters at rest, during restraint stress and during recovery. Basal haemodynamic parameters were similar in the different groups but the pattern of cardiovascular responses during stress and recovery differed markedly between prenatally stressed (PS) and control animals. PS rats had higher and longer-lasting systolic arterial pressure elevations to restraint stress than control animals. They also showed elevated systolic and diastolic blood pressure values during the recovery phase. PS rats demonstrated a greater increase in blood pressure variability compared with control animals during exposure to restraint stress, and showed more prolonged heart rate responses to acute stress and delayed recovery than controls. There was no effect of prenatal stress on baroreflex regulation of heart rate. PS females showed a greater increase in systolic arterial pressure and blood pressure variability and delayed heart rate recovery following return to the home cage then did PS males. These findings demonstrate for the first time that prenatal stress can induce long-term, sex-related changes in the sensitivity of the cardiovascular system to subsequent stress.

[Effect of prenatal hyperandrogenism during pregnancy and on postnatal development of rats]. / Vplyv prenatal'noï hiperandrohenizatsiï na perebih vahitnosti ta pislianatal'nyi rozvytok shchuriv.

Hyperandrogenia was modelled in the female rats within the whole term of pregnancy by means of testosterone or dihydrotestosterone. Both androgens have been established to induce significant prenatal mortality and high percentage of mortinatus and postnatal mortality of progeny. Hyperandrogenization influenced negatively the sexual development and reproductive function of the female progeny versus the male one.

Effects of collagenolytic protease preparations from invertebrates on the immune system.

We studied the effects of an active ingredient of new enzyme preparations containing collagenolytic proteases from various hydrobionts (Collagenase from hydrobionts, Polycollagenase-K, and Fermenkol). These substances in therapeutic doses did not affect the humoral immune response estimated by hemagglutination and local hemolysis in gel and caused no local irritation and allergic reactions after long-term application to the skin.

Collagenolytic protease preparations from invertebrates: experimental study of acute and chronic toxicity.

Toxicity of active matter of new structure-destroying enzyme preparations containing a complex of collagenolytic proteases from invertebrates (Collagenase from hydrobionts, Polycollagenase-K, Fermenkol) was studied. The absence of acute toxicity in skin application is proved, and LD(50) for intraperitoneal administration to mice and rats were determined. A long-term treatment with clinical doses under various types of application does not affect body weight gain, biochemical indices of the plasma, ECG, diuresis, and urine content.

Collagenolytic protease preparations from invertebrates: biochemical aspects of medical and cosmetological applications.

Collagenolytic proteases from invertebrates, the active matter of new structure-destroying enzyme preparations (Collagenase from hydrobionts, Polycollagenase-K, Fermenkol), ensure deep hydrolysis of polypeptide substrates (native or partially denatured collagen types, elastin, fibrin, hemoglobin, and casein) that cannot be attained by collagenases and serine proteases. Biochemical properties of collagenolytic proteases from invertebrates, techniques and doses that may be important for elaboration and employment of preparations based on this complex are described.

The preparation of soft-tritium-labelled proteins and their application for the collagenolytic activity investigations.

Tritium-labelled Type I collagen from rat skin with specific activity of 8 mCi/mg and mixture of the crab hepatopancrease collagenolytic enzymes with specific activity of 25 mCi/mg have been obtained by the method of high-temperature solid-state catalytic isotope exchange (HSCIE) without loss of native features. Tritium-labelled Type I collagen kept its ability to form native fibrils being resistant to trypsin hydrolysis. Tritium-labelled collagenase keeps about 70% of its proteolytic activity.

[Vitamin D and calcium metabolism in relation to different levels of vitamins B6 and D]. / Obmen vitamina D i kal'tsiia pri razlichnoi obespechennosti vitamina B6 i D.

The influence of vitamin B6 deficiency on some vitamin D-dependent processes was studied in animals. The following parameters changing in relation to the level of vitamin D providing were investigated: activity of alkaline phosphatase in the serum and small intestine mucosa, the levels of Ca, P and parathormone, concentration of vitamin D metabolites and enzyme activity; and only 25-hydroxyvitamin D (25-OVD) concentration in the blood serum, under conditions of combined vitamin B6 and D deficiency was significantly lower as compared to cases with vitamin D deficiency alone. In the presence of vitamin B6 deficiency recovery of 25-OVD level in the blood serum, after vitamin D administration to the animals, had a tendency to delay as compared to that in the animals provided with vitamin B6. Vitamin B6 deficiency produced similar effect on 25-OVD 1-hydroxylase activity. The data obtained have evidenced a possibility of vitamin B6 influence on vitamin D metabolism.