Chronic endometritis: prevention and treatment options

This article is a review of publications devoted to the treatment of chronic endometritis and methods of its prevention. Methods of empiric therapy, standards of antibacterial therapy, and modern guidelines for treatment under development (colonystimulating factor, immunotherapy, amplipulse therapy) are presented. Key words: infertility, miscarriage, colony-stimulating factor, chronic endometritis, cytokine therapy

Immunogenicity Assessment of Pegfilgrastim in Patients with Breast Cancer

Introduction. Neutropenia, which is an abnormally low concentration of neutrophils in the blood, is one of the common side effects in patients receiving radio- or chemotherapy. Neutropenia usually leads to higher risks of severe bacterial and fungal infections. Such medicines as colonystimulating factor filgrastim (and its conjugates) are used to prevent and treat neutropenia in oncology patients. Immunogenicity is a potential concern for any biological product, thus, its assessment is one of the most critical necessities during the development and registration of such products.Aim. The main aim of this study was to validate the ELISA method for anti-pegfilgrastim antibodies detection in human serum samples and to apply the validated method to pegfilgrastim drugs immunogenicity assessment.Materials and methods. To assess pegfilgrastim immunogenicity, the commercial ELISA kit «PEGylated Filgrastim (Neulasta®) ADA ELISA» was used for screening, confirmatory and titer assay. Moreover, to confirm the chosen commercial kit suits the study aims it was revalidated. The absorbance values were obtained using plate immunoassay analyzer Stat Fax 3200, plate washing was performed using an automatic twochannel plate washer.Results and discussion. The ELISA method for anti-pegfilgrastim antibodies determination in human serum samples was validated and applied to the analytical part of the comparative, multicenter, blind, randomized study of pegfilgrastim efficacy and safety in patients with breast cancer, receiving myelosuppressive chemotherapy. Human serum samples were first screened for anti-drug antibodies, then «screening positive» samples were analyzed in confirmatory assay with % inhibition calculation for each sample. The «confirmed positive» samples were further characterized in titer assay.Conclusions. The ELISA method for anti-pegfilgrastim antibodies determination in human serum samples was successfully validated and applied for pegfilgrastim drugs immunogenicity assessment.

Bone pain associated with rhG-CSF or PEG-rhG-CSF in oncology patients.

e19186 Background: Recombinant human granulocyte colonystimulating factor (rhG-CSF) and glycoPEGylated G-CSF (PEG-rhG-CSF) are two kinds of drugs in reducing the incidence and duration of neutropenia in oncology patients treated with chemotherapy. Although the acting time is different, bone pain is one of the most common adverse events in rhG-CSF and PEG-rhG-CSF. The purpose of this study is to describe the occurrence and management of bone pain in oncology patients receiving rhG-CSF and PEG-rhG-CSF. Methods: Two hundred and forty patients with malignant tumor received rhG-CSF or PEG-rhG-CSF after chemotherapy were enrolled to finish questionnaires about the side effect of bone pain. The incidence, location, duration, degree and treatment of bone pain after rhG-CSF or PEG-rhG-CSF used were collected and analyzed. Results: A total of 240 patients enrolled and 56.3% (135) patients had bone pain after rhG-CSF or PEG-rhG-CSF delivered. The most common parts of bone pain were thigh (35.6%), back (29.6%), waist (25.9%), shoulder (23.7%) and chest (21.5%). The bone pain of 39.2% patients last for 72h and 27.2% patients last less than 72h. The duration time of bone pain was longer in PEG-rhG-CSF than rhG-CSF. There was no significant difference in the rate of pain occurrence and the proportion of severe pain between rhG-CSF and PEG-rhG-CSF. Only 22.2% patients took drugs to relieve bone pain. Downregulated the doses of rhG-CSF or PEG-rhG-CSF could significantly relieve bone pain. Besides bone pain, 34.0% patients suffered muscle ache which was the second most side effect and occurred more often than runny nose and fever. Conclusions: The percentage of bone pain occurrence are similar in rhG-CSF and PEG-rhG-CSF, but the duration time was longer in PEG-rhG-CSF. For most patients, bone pain need not to deal with, Dose reductions can effectively relieve the mild to severe pain.

PROSPECTIVE METHODS FOR CORRECTION OF NEUROTOXIC IMPAIRMENTS CAUSED BY SEVERE CARBON MONOXIDE POISONING (REVIEW)

The review sets forth perspective directions of correction of neurotoxic disorders in case of carbon monoxide damage. It was shown that carbon monoxide intoxication, in addition to the development of hemic hypoxia, leads to indirect lesions in the structures of the central nervous system that develop both in the early and delayed periods of poisoning. Those lesions can be caused by the development of oxidative stress, activation of programmed cell death, impact on the intercellular signaling system etc. There is evidence that oxygen monotherapy does not lead to a complete recovery of cognitive functions in a delayed period of severe carbon monoxide poisoning. It was found out that to correct central nervous system functions disorders in case of acute damage by carbon monoxide, it is necessary to use agents possessing neuroprotective mechanisms of action. The review reports data on the effectiveness of hydrogenated solution, methane solution, allopurinol, erythropoietin, granulocyte colonystimulating factor, remifentanil, mesenchymal stem cells, cerebrolysin for correction of the central nervous system disorders in this type of pathology.

PREVENTION OF MYELOSUPPRESSION BY COMBINED TREATMENT WITH ENTEROSORBENT AND GRANULOCYTE COLONY-STIMULATING FACTOR

Hematotoxicity and its complication are the prominent limiting factors for rational treatment of malignancies. Granulocyte colonystimulating factor (G-CSF) is used to increase granulocyte production. It has been shown previously that enterosorption causes prominent myeloprotective activity also. Still, no trial was performed to combine both of them. Aim: To study the influence of combination of enterosorption and pharmaceutical analogue of naturally occurring G-CSF (filgrastim) on bone marrow protection and the growth of grafted tumor in a case of injection of melphalan (Mel). Materials and Methods: Mel injections were used for promotion of bone marrow suppression in rats. Carbon granulated enterosorbent C2 (IEPOR) was used for providing of enteral sorption detoxifying therapy. Filgrastim was used to increase white blood cells (WBC) count. Results: The simultaneous usage of enterosorption and filgrastim had maximum effectiveness for restoring of all types of blood cells. WBC count was higher by 138.3% compared with the Mel group. The increase of platelets count by 98.5% was also observed. In the group (Mel + C2 + filgrastim) the absolute neutrophils count was twofold higher, in comparison with rats of Mel group. Conclusion: Simultaneous admin istration of G-CSF-analogue and carbonic enterosorbent C2 is a perspective approach for bone marrow protection, when the cytostatic drug melphalan is used. Such combination demonstrates prominent positive impact on restoring of all types of blood cells and had no influence on the antitumor efficacy.

Primary pulmonary alveolar proteinosis

Introduction. Pulmonary alveolar proteinosis is an uncommon disease characterized by the accumulation of surfactant proteins and phospholipids within the alveolar spaces. Acquired disease can be idiopathic (primary) and secondary. The prevalence of acquired pulmonary alveolar proteinosis is about 0.37 per 100,000 persons. Common symptoms are dyspnea and cough. Chest X-ray shows bilateral perihilar infiltrates. Open-lung biopsy is the gold standard for the diagnosis. Treatment includes whole-lung lavage, application of granulocyte-macrophage colonystimulating factor and lung transplantation. Case report. We reported a 51 year-old man with primary form of the disease. It was the second case of this extremely rare disease in the past 30 years in our clinic. The symptoms were longlasting dry cough, fever and physical deterioration. Chest Xray revealed bilateral pulmonary infiltrates; computed tomography showed patchy ground-glass opacification with interlobular thickening. The diagnosis was established by open lung biopsy. Additional tests were performed to exclude secondary form of the disease. Conclusion. We presented a rare clinical entity with typical clinical features and clinical and radiological course of the disease, in order to improve differential diagnostic approach to patients with bilateral lung infiltrations. In patients with pulmonary alveolar proteinosis timely diagnosis and adequate treatment can improve a prognosis.

Mobilization of hematopoietic stem cells during homeostasis and after cytokine exposure

We created parabiotic mice, joining ROSA26 and PeP3b animals, to study the trafficking of hematopoietic stem cells (HSCs) from marrow to blood and their return to marrow. The transfer of HSCs was assayed by secondary marrow transplantation and was 1.0% to 2.5% after 3, 6, 8, and 12 weeks. Thus, HSC homeostasis is primarily maintained by the retention of stem cells derived from replication events within the marrow, not the homing and engraftment of HSCs from the circulation. Of interest, the phenotypes of marrow progenitors and granulocytes were similar to those for HSCs, implying that the marrow functions as an intact compartment where differentiating cells derive from endogenous HSC. In contrast, 50% of splenic granulocytes and progenitor cells derived from the parabiotic partner, suggesting splenic progenitor cells were in constant equilibrium with progenitors in blood. In additional studies, animals were exposed to granulocyte–colonystimulating factor (G-CSF) and stem cell factor at days 17 to 20 of parabiosis and were studied 3 weeks later; 10.1% of marrow HSCs derived from the parabiotic partner. These data imply that HSCs, mobilized to the blood in response to cytokine exposure, are destined to later return to marrow, an observation that supports the concept that the mobilized peripheral blood stem cells used in clinical transplantation function physiologically.