Biodegradable pH-sensitive prospidine-loaded dextran phosphate based hydrogels for local tumor therapy.

The paper focuses on the development of drug delivery systems based on hydrogels of dextran phosphate (DP) for local cancer therapy. The hydrogels were characterized by physicochemical properties including functional group content, morphology, gel fraction, pH-responsive swelling. The desirable pH-sensitive drug release behavior of these hydrogels was demonstrated by a drug release test with Prospidine-loaded hydrogels (DP-Pr hydrogels) at different pH values. In vitro degradation of the DP-Pr hydrogels was determined under simulated physiological conditions. The cytotoxicity of the blank DP hydrogels and DP-Pr hydrogels with different Pr concentrations was evaluated with HeLa and HЕр-2 cells. Investigations of antitumor efficiency in vivo showed that administration of DP-Pr hydrogels in comparison with an aqueous solution of Pr results in the increase of antitumor activity, prolongation of therapeutic action and growth of a number of animals cured. Therefore, such pH-responsive DP hydrogels could be promising candidates as drug delivery carriers.

Serial assessment of spot urine sodium predicts effectiveness of decongestion and outcome in patients with acute heart failure.

AIMS: The clinical significance of the measurement of urine sodium concentration (UNa+ ) in response to loop diuretic administration in patients with acute heart failure (AHF) is still unsettled. We studied the association of serial measurements of spot UNa+ during the first 48 h of AHF treatment with the indices of decongestion, renal function, and prognosis. METHODS AND RESULTS: We enrolled 111 AHF patients, all of whom received intravenous furosemide on admission. The mean spot UNa+ significantly increased in the 6 h sample (P < 0.05 vs. baseline) and returned to baseline values in the 24 and 48 h samples. Based on the increase or decrease/no change of UNa+ in the 6 and 48 h samples vs. baseline, patients were divided into two groups at each time point, respectively. Patients did not differ in baseline clinical and laboratory characteristics. Patients with a decrease/no change of UNa+ in the 6 and 48 h samples had a lower weight loss during hospitalization. Patients with a decrease/no change of UNa+ in the 48 h sample had a poorer diuretic response and a significant increase in the urinary levels of the tubular biomarkers: kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin. Low UNa+ and decrease/no change in UNa+ in the 6 and 48 h samples were independent predictors of higher risk of all-cause mortality during 1-year follow-up (all P < 0.05). CONCLUSION: In AHF, low spot UNa+ and lack to increase UNa+ in response to intravenous diuretics are associated with poor diuretic response, markers of tubular injury and high risk of 1-year mortality.

[Antineoplastic effect of hydrogel prospidin on Seidel ascites hepatoma used as a model].

Antineoplastic effect of hydrogel dextran phosphate, hydrogel prospidin, and prospidin in an injectable preparation has been assessed using Seidel ascites hepatoma as a model. Injectable and hydrogel prospidin in doses from 250, 500 to 1000 mg/kg and hydrogel phosphate dextran in doses of 500 and 1000 mg/kg were administered to rats intraperitoneally in a single dose in a volume of 1 or 2 ml per each 100 g of animal body weight. The study has shown that irrespective of rats with Seidel ascites hepatoma and significantly increase in the dosage of prospidin preparations and hydrogel dextran phosphate results in a longer average life expectancy of rats Compared with its injectable variant, hydrogel prospidin appears to produce more than twice as high antineoplastic effect, and is found to provide prolonged therapeutic effects, as well as cure of animals in more than 60 % of cases.

One-year surveillance of methicillin-resistant Staphylococcus aureus nasal colonization and skin and soft tissue infections in collegiate athletes.

OBJECTIVE: To determine the frequency and clinical importance of methicillin-resistant Staphylococcus aureus (MRSA) colonization in student athletes. DESIGN: Prospective observational cohort study. SETTING: A major university in the southeastern United States. PARTICIPANTS: Student athletes participating in the men's football and women's lacrosse programs (N = 126). Main Exposure Monthly assessment of S aureus nasal colonization. MAIN OUTCOME MEASURES: Trends in S aureus colonization over time and the occurrence of skin and soft tissue infections. RESULTS: Methicillin-resistant S aureus nasal colonization varied significantly through the athletic season (4%-23%), peaking during times of highest athletic activity. This increase in colonization was not associated with the development of an outbreak of skin and soft tissue infections, and no single MRSA clone emerged as a dominant isolate. CONCLUSIONS: During the athletic season, there is a considerable burden of MRSA colonization in student athletes; however, colonization alone appears to be insufficient to trigger an outbreak of staphylococcal infections. A combination of distinct molecular characteristics in the organism and specific host factors may govern the development of staphylococcal disease.

Comparison of the different types of "laparoscopic total hysterectomy".

STUDY OBJECTIVE: To review the operative outcomes among different types of laparoscopic total hysterectomy (LH) classified according to the Munro and Parker classification system. DESIGN: Prospective observational cohort study (Canadian Task Force classification II). SETTING: 6 major public hospitals in Hong Kong. PATIENTS: 143 patients underwent LH in a 6-month period. INTERVENTIONS: Type I to type IV LH according to the Munro and Parker classification system. MEASUREMENTS AND MAIN RESULTS: We studied 56 type I, 49 type II, 25 type III, and 13 type IV LH. The median operative time was 105 minutes, which was significantly longer in the type IV LH group (160 minutes). The median blood loss was significantly higher in the type I LH group (300 mL). The incidence of urinary tract infection in type I LH was 8.9%, which was significantly higher than other LH groups. The overall operative complication rate was 20.3%, which was highest in the type III hysterectomy group (36%), although the difference did not reach statistical significance among the various types of hysterectomy groups. CONCLUSION: There has been a change from abdominal hysterectomy to LH in the past decades, and it is time for us to explore the best type of LH. Our findings suggest that type I LH is associated with significantly more blood loss and urinary tract infection; whereas type IV LH is associated with significantly longer operating time. However, we still cannot conclude which is the best type of LH until results from a randomized controlled trial will become available.

[Psoriatic arthritis: combined treatment with prospidin and methotrexate].

AIM: To compare clinical efficacy of methotrexate monotherapy and methotrexate combination with prospidin in patients with psoriatic arthritis (PA). MATERIAL AND METHODS: Sixty three patients (42 females and 21 males) with documented PA, generalized articular syndrome of the second-third degree of activity were divided into two groups. Patients of group 1 (n = 30) received combined therapy (i.v. prospidin 200-300 mg/week + i.m. methotrexate 10 mg/week). Maintenance consisted of prospidin in a dose 100-200 mg/week i.m., methotrexate dose was the same. Patients of group 2 (n = 33) were given methotrexate monotherapy in a dose 10 mg/ week i.m. RESULTS: In the first three months of the study and in maintenance therapy, combined treatment was more effective. By ACR criteria, 50-70% response was achieved after 12 months of treatment in 44 and 27.3% patients of groups 1 and 2, respectively. The number of side effects and drug-related withdrawals was 23.3 and 36.4%, 10 and 15.1% in groups 1 and 2, respectively. CONCLUSION: Combination of methotrexate with prospidin produced an earlier and more potent positive clinical effect than methotrexate alone in PA patients.

[Clinical and morphological characteristics of laryngeal papillomatosis in children].

Respiratory papillomatosis was studied clinically and morphologically in 35 children with immunohistochemical detection of human papilloma virus. More frequent detection of viral antigen in the superficial layers of the epithelium in children with frequent recurrences was observed. Correlation between clinical efficiency of prospidine and immunohistochemical findings was noted. Suggestion on the indirect link between viral damage and intranuclear inclusions (although viral antigen in these inclusion was not observed) was made.

Primary cutaneous plasmacytoma: a clinicopathological study of two cases with a long-term follow-up and review of the literature.

BACKGROUND: Primary cutaneous plasmacytoma (PCP) is a rare type of cutaneous B-cell lymphoma arising primarily in the skin and derived from clonally expanded plasma cells with a various degrees of maturation and atypia. The disease is rare with only 30 cases reported so far. METHODS: Two cases of PCP with long-term follow-up of 17 and 15 years are presented. RESULTS AND CONCLUSIONS: Both patients were men with nodular lesions on the face. Histologically, the lesions were composed predominantly of variably maturated plasma cells with monotypic expression of immunoglobulin (Ig) lambda chains. Polymerase chain reaction for IgH genes did not reveal clonal rearrangement. Our cases are discussed in the context of previously reported cases of PCP with a long-term follow-up. We also include a review of all cases of PCP with known tumor progression earlier in the course of the disease (local relapse or visceral spread) to determine the clinical course of this primary cutaneous lymphoma.

[Phagocytic activity of mouse peritoneal macrophages under administration of bacterial vaccines and prospidin]. / Fagotsitarnaia aktivnost' peritoneal'nykh makrofagov myshei pri vvedenii bakterial'nykh vaktsin i prospidina.

Phagocytic activity of peritoneal macrophages in cases of separate and combined injections of killed bacterial vaccines and prospidin has been studied in the work. As a result of researches conducted, it has been found out that the injection of vaccines together with prospidin makes it possible to reduce an inhibiting effect of prospidin on phagocytic activity of monocyte-macrophagal cells; first of all it concerns their digestive activity. Thus, the immunodepressing effect of antiblastome drugs may be reduced with the help of injection of killed bacterial vaccines which stimulate nonspecific factors of organism protection, including antineoplastic ones.

[3',5'-cAMP phosphodiesterase inhibitors in the combined treatment of patients with rheumatoid arthritis]. / Inhibitory 3'--5'-tsAMF-fosfodiiesterazy v kompleksnomu likuvanni khvorykh na revmatoïdnyi artryt.

A study was made of clinical effectiveness and mechanism of action of the inhibitor of the specific 3',5'-cAMP phosphodiesterase papaverine in a therapeutic complex of measures designed to treat RA patients involving an immunodepressive preparation free from any cytopenic effect prospidin as a basic mediator. It has been shown that the papaverine antiarthritic action is associated with its positive effects on the unspecific component of the immune-complex inflammation, viz. processes of lipid peroxidation, activity of the antioxidant system of defence as well as on the vascular tone and microcirculation. All this improves tissue metabolism, and in this way enhances efficiency of RA basic therapy.

[Pulse therapy with prospidin and methotrexate: comparative efficacy in rheumatoid arthritis (12-month controlled study)]. / Sravnitel'naia éffektivnost' pul's-terapii prospidinom i metotreksatom pri revmatoidnom artrite (12-mesiachnoe kontroliruemoe issledovanie).

Efficiency of pulse-therapy with prospidin (500 mg for 5 days in hospital, 500-1000 mg for a month as maintenance) and methotrexate (30 mg a week i.v. in hospital, 7-10 mg a week as maintenance) was investigated in 93 patients with severe RA. The response to prospidin and methotrexate arose quickly (within 10-14 and 4-5 weeks, respectively) and occurred in 73 and 70% of patients, respectively. Withdrawal of the drug was caused by side effects of methotrexate (19.3%) and resistance to prospidin (23.2%).

[Use of adjuvant therapy in patients with metastasis of melanoma to regional lymph nodes]. / Primenenie ad"iuvantnoi terapii u bol'nykh s metastazami melanomy v regionarnykh limfaticheskikh uzlakh.

The results of treatment of 276 patients with cutaneous melanoma of T1-4N1M0 stage were analyzed. The irradiation therapy conduction did not influence the result of surgical treatment. The trustworthy improvement of three-year survival index of patients after the radical operation conduction was noted under the influence of the endolymphatic cytostatic therapy. The result of preoperative endolymphatic chemotherapy and interferon therapy conduction is quite similar.

[Local use of polymer-based cytostatic agents in surgical treatment of patients with laryngeal cancer]. / Mestnoe ispol'zovanie tsitostatikov na polimernoi osnove pri operatsiiakh u bolnykh rakom gortani.

To improve the outcomes of surgical or combined treatment of patients with laryngeal cancer stage III-IV in terms of preventing the recurrences and metastases, the authors placed biocompatible polymer material saturated with cytostatic in the operative wound in the end of the surgical intervention. The response assessed in 107 patients with laryngeal cancer treated with prospidin on polymer film (20 cases) versus 87 prospidin-untreated controls was more positive in the test group (5-year survival was higher).

[Transitional laryngeal papilloma: clinical aspects, diagnosis and treatment]. / Perekhodnaia papilloma gortani (osobennosti kliniki, diagnostika, lechenie).

Basing on the results of long-term observational study of 200 patients with laryngeal papillomatosis the authors made a conclusion on cycle pattern of the disease course. Each cycle consists of two periods: active (rapid growth of the tumor) and passive (slow growth of the tumor, recurrences are rare, 1-3 years of remission). A case of a male patient is reported illustrating cycle course of transitional laryngeal papilloma. In the beginning of the third cycle, in active period, his papilloma underwent malignant transformation. Cryotherapy of papilloma is thought ineffective.

[Use of immunomocorrection in the combined treatment of laryngeal papillomatosis in children]. / Ispol'zovanie sredstv immunokorrektsii v kompleksnom lechenii papillomatoza gortani u detei.

Original immunological studies allowed the authors to design a combined treatment of laryngeal papillomatosis (LP) with administration of immunomodulators and cytostatics. Surgery was performed on demand. Thymic hormone preparation (T-activin, thymalin, thymogen) and prospidin served as immunomodulators and cytostatic, respectively. To create lymphotropism, prospidin was delivered by means of electrophoresis following subcutaneous introduction of 8--16 U lidase. Sensitivity of patients to thymalin was tested in vitro by thymalin-induced changes in the number of CD2--DR+ lymphocytes. Adjuvant modalities were age-adjusted dibasol as inductor of interferon genesis and adaptogens (eleutherococcal fluid extract, B and C vitamins). Such treatment was given to 39 children. Remission duration increased 1.6--2.6-fold, 6 of 7 children with primary LP achieved persistent remission. Positive changes in immunological indices occurred in 84% of children. The above treatment outcomes support the efficacy of the method in childhood LP.

[Hormonal-metabolic and immune status in recurrent laryngeal papillomatosis in children]. / Gormonal'no-metabolicheskii i immunnyi statusy pri retsidiviruiushchem papillomatoze gortani u detei.

Clinical, biochemical and immunological findings in 12 children with recurrent laryngeal papillomatosis evidence for defects in hormonal--metabolic and immune profiles in terms of depressed sympathoadrenal, adrenocortical functions and secondary immunodeficiency. To correct the above disorders it is advisable to practice immunocorrective therapy and drugs (prospidin) stimulating adrenal function.

Determination of the anticancer drug prospidin in human tissue by high-performance capillary electrophoresis using derivatization.

A high-performance capillary electrophoresis (HPCE) method is described for the quantitative determination of the anticancer drug prospidin in human tissue after its derivatization with diethyldithiocarbamic acid sodium salt (DDTC). It was found that absorption of prospidin and its derivatives on the capillary wall due to the strong positive charge in the drug molecules could be eliminated by increasing the methanol content in the run buffer up to 50% and increasing the pH value up to 11.2. While studying the conditions of the interaction between prospidin and DDTC, a molar excess of the latter of 1:9 and 1.5 h of reaction time were found to be enough for complete derivatization. Sample preparation included homogenization of freshly cut papilloma species and deproteinization by methanol addition. Detection was by ultraviolet (UV) absorption at 254 nm. Due to its speed and high performance in separation, HPCE was found to be well suited for the fast checking of drug therapy in clinical practice.

[Use of time-of-flight mass spectrometry with ionization division fragments of californium-252 for studying the mechanisms of action of drugs on DNA and its components]. / Primenenie vremia proletnoi mass-spektrometrii s ionizatsiei oskolkami deleniia kaliforniia-252 k izucheniiu mekhanizmov deistviia lekarstvennykh preparatov na DNK i ee komponenty.

Using soft-ionization mass spectrometry (252-Cf particle desorption mass spectrometry, PDMS) a minor adduct of anticancer drug prospidine and deoxyguanosine-5-phosphate (pdG) has been found. It has been shown experimentally that PDMS is very useful for study of biological mixtures as well as mechanisms of interactions between drugs and biomolecules.