High Therapeutic Effect Research Articles

An RNAi therapeutic, DFP-10825, for intraperitoneal and intrapleural malignant cancers.

RNA interference (RNAi), a potent post-transcriptional gene-silencing action, has received considerable attentions as a novel therapeutic tool to treat intractable cancers. In recent days, we have developed a novel RNAi-based therapeutic formulation, DFP-10825, for the treatment of intractable advanced cancers developed in coelomic cavities. DFP-10825 was composed of chemically synthesized short hairpin RNA (shRNA) against thymidylate synthase (TS), a key enzyme for cancer proliferation, and cationic liposomes, and achieved high therapeutic effect on the mouse models of peritoneally disseminated gastric and ovarian cancers and malignant pleural mesothelioma without severe side effects by intracoelomic direct treatment. We further designed a freeze-dried DFP-10825 formulation for mass industrial production. DFP-10825 is undergoing in pre-clinical phase and goes to clinical trials. This review introduces a DFP-10825 formulation, a potent novel RNAi-based therapeutic maximizing the benefit of RNAi molecule (shRNA).

ОСТРАЯ ТОКСИЧНОСТЬ И СРАВНИТЕЛЬНАЯ ТЕРАПЕВТИЧЕСКАЯ ЭФФЕКТИВНОСТЬ ЛЕВОФЛОКСАЦИНА ПРИ ЭКСПЕРИМЕНТАЛЬНОМ КОЛИБАКТЕРИОЗЕ ЦЫПЛЯТ

Development and improvement of treatment modes for colibacillosis in chickens is very important as this disease is rather prev-alent in bird population. Fluoroquinolones are drugs that are very effective in treating bacterial infections, associated with Gram- negative microorganisms, in animals. The goal of the present research was to evaluate acute toxicity of Levofloxacin in chickens and to study its comparative therapeutic effi-cacy in experimental colibacillosis of chick-ens. For the experiment aimed at evaluating acute toxicity of Levofloxacin all the chick-ens were assigned to a total of 18 groups, 10 chickens were assigned to each group. The drug was administered by intraperitoneal injection at a dose of 100 to 950 mg/kg body weight. In our research median lethal dose (LD50) of Levofloxacin, in case of intraperi-toneal introduction to chickens, was as high as 470 mg/kg body weight (276.4–799 mg/kg body weight). For the experiment aimed at studying comparative therapeutic efficacy of Levofloxacin in experimental colibacillosis all the chickens were assigned to a total of 8 groups, 25 chickens were assigned to each group. In the course of the experiment every chicken was challenged with Escherichia coli, by intraperitoneal introduction of 150 million CFUs (E. coli had been cultured in suspension for 24 hours). Antimicrobial drugs (Levofloxacin, Enrofloxacin, Colistin, Ditrim, Doxycycline, Chloramphenicol) were first administered 24 hours before the challenge, at a concentration of 200 mg/L, via drinking water. The treatment continued 5 days. The chickens were monitored 3 weeks. The results of the experiments show the high therapeutic effect in cases of Levofloxacin (100%) and Enrofloxacin (92%). Administration of other antimicrobial drugs did not lead to the expected results. The survival rate was in the range 12 to 20%

Morphological parameters of blood of calves with cryptosporidiosis after applying different treatment regimens

Recently the livestock farmers of Baltasinsky, Kukmorsky, Sabinsky, Alkeevsky and other regions of the Republic of Tatarstan have increasingly frequently faced the young cattle diseases associated with pathology of the gastrointestinal tract that have not been treated by the classical scheme of diseases with diarrhea symptoms.Sick calves had acute and subacute catarrhal gastroenteritis mainly in the later stages of which accompanied by the inflammatory process in the posterior segment of the small intestine. The manifestations of structural changes in the subepithelial lymphoid tissue of the intestine, in the stagnant digestive glands and regional lymph nodes were increased with a severity level of the clinical symptoms of the disease.In this regard, in order to obtain a complete picture of the effect of cryptosporidiosis invasion on the peripheral blood condition of sick calves, hematological studies were conducted in the dynamics of the development of the infectious process. We have studied the content of red blood cells, white blood cells including lymphocytes, granulocytes, as well as monocytes and hemoglobin on the 7th, 14th and 30th days of the experiment. Hematological studies of calves infected with spontaneous invasion of cryptosporidiosis, and after treatment, had been carried out in 2016 2018 at the OJSC “KukmorAgroChimService” in the Kukmorsky district of the Republic of Tatarstan in the Russian federation. Cryptosporidiosis clinically insane calves had erythropenia and leukocytopenia in the blood and low hemoglobin. Reduced oxygen capacity of the blood contributed to the development of the secondary destructive changes in the organs of hematopoietic organs. The established dynamics of a decrease in the content of eosinophilic granulocytes in the blood of calves in the first and especially in the second groups indicated a high therapeutic effect of the drugs used. Starting from the 7th day, due to the therapeutic effect of the tested medications in the places of the pathogenic effects of cryptosporidia, regenerative processes were intensified. It affected the morphological parameters of the blood.

ДОСЛІДЖЕННЯ МОЖЛИВОСТІ ПІДВИЩЕННЯ РАЦІОНАЛЬНОСТІ ПЛАНОВИХ ЗАГОТІВЕЛЬ ЛІКАРСЬКОЇ РОСЛИННОЇ СИРОВИНИ ДЛЯ ЗАБЕЗПЕЧЕННЯ ЯКОСТІ ФІТОРЕАБІЛІТАЦІЇ ВІЙСЬКОВОСЛУЖБОВЦІВ

Keywords: wild medicinal plants, phyto-raw materials, dosage form, themilitary, rehabilitation, regions of Ukraine. The aims of the research were theoretical substantiation of scientific and practical approach to detection and analysis of distribution of wild medicinal plants with significant resource potential in regions of Ukraine and development of a theoretical platform for substitution therapy during the rehabilitation that based on the generalization of information on domestic floristic resources. The authors structured and fragmentarily presented information about botanical and geographical zoning of medicinal plants with a significant raw material resource for each of the 25 regions of Ukraine as an element of their natural and recreational potential that may be use as a replacement therapy for military medicine. The leading regions are identified in terms of the total number and diversity of species, the volume of raw materials. Attention was focused on 40 wild medicinal plants, the most common in each region.The relationship between the chemical composition and treatment and prevention of certain plants, possible dosage forms and directions of pharmacotherapeutic action have been studied. Significant advantage of infusions and decoctions (made on water or milk) of anti-inflammatory, wound-healing, analgesic, antipyretic, hemostatic action is revealed.Emphasis is placed on the high therapeutic effect of phytomedicines in the treatment of purulent wounds, burns, ulcers, abscesses, fistulas;opportunities to accelerate regeneration processes. Comparative phytoanalysis allowed to unify 10 medicinal plants with a wide raw material resource in the vast majority of regions of the country.A sample of possible formulations of extemporaneous and industrial production is made, the general technological principles of their production are analyzed. The collected material will significantly adjust the plans for possible procurement of vegetable raw materials for the needs of military medicine.

A method to selectively internalise submicrometer boron carbide particles into cancer cells using surface transferrin conjugation for developing a new boron neutron capture therapy agent

With the goal of developing a new type of boron neutron capture therapy (BNCT) agent, selective internalisation of submicrometer boron carbide spherical particles into cancer cells via surface transferrin conjugation is demonstrated and confirmed in vitro and in vivo. Herein, negatively charged, spherical, submicrometer boron carbide (B4C) particles were coated with positively charged poly-L-lysine and negatively charged poly-γ-glutamic acid; the particles were subsequently conjugated with transferrin. It was confirmed in vitro and in vivo by confocal laser scanning microscopy and transmission electron microscopy that the coated particles interacted with transferrin receptors that were highly expressed on the surface of cancer cells, endocytosed by tumour cells, and transferred to the proximity of the nucleus. The submicrometer size of the particles provided stronger interaction between transferrin and transferrin receptors and hence resulted in more efficient internalisation than that obtained using nanoparticles. This method might be effective for the selective internalisation of large submicrometer particles for high therapeutic effects due to the large particle size, but with small particle dosages.

Encapsulation of curcumin loaded chitosan nanoparticle within poly (ε-caprolactone) and gelatin fiber mat for wound healing and layered dermal reconstitution

Hybrid electrospun fiber containing bioactive molecules, which offer the ability to deliver the cells into the wound bed, will help to achieve a high therapeutic effect. In this study, an electrospun polycaperlactone (PCL) and gelatin (Gela) scaffold containing curcumin loaded chitosan nanoparticle (NCs/Cur) was used to evaluate in vivo wound healing ability of the fabricated scaffolds. The electrospun hybrid scaffold seeded with human endometrial stem cells (EnSCs) showed desirable biocompatibility with the host immune system and wound healing ability in a full-thickness excisional animal model. The constructs were characterized for structural, mechanical and biochemical properties. Fourier transform infrared spectroscopy (FTIR) confirmed all typical absorption characteristics of PCL and Gela polymers as well as NCs and Cur. The results showed the perfect contact angle, wettability and degradability of hybrid fiber scaffolds with the good mechanical and structural characteristics including shape uniformity, pore size and porosity. The cell attachment and proliferation on the PCL/Gela/NCs/Cur was higher than PCL and PCL/Gela scaffolds. In term of the capability of hybrid scaffold and EnSCs in histological analysis, this novel tissue-engineered construct could be suggested as a skin substitute to repair injured skin and regenerative medicine application.

Оценка терапевтической эффективности суспензии «Празител® Особый» при кишечных гельминтозах щенков и котят

The effectiveness of the anthelmintic drug «Prazitel® Specialis suspension» for dogs and cats over 6 years of age in puppies and kittens with intestinal worm infection was studied. Suspension Prazitel® Specialis refers to low-hazard substances (hazard class IV according to GOST 12.1.007-76), contains a unique active substance R-praziquantel in combination with pyrantel pamoat and silybin.
 
 Efficiency of «Prazitel® Specialis suspension» for dogs weighing up to 5 kg after double oral administration to puppies at a dose of 1.0 ml/kg BW, which corresponds to a dose of R-praziquantel 1.5 mg/kg, pyrantel pamoate 15.0 mg/kg and silybin 1.7 mg/kg for toxocariasis, hookworm infection, dipylidiosis, teniosis and mixed invasion was 100 %. The effectiveness of «Prazitel® Special suspension» for dogs weighing from 5 to 25 kg after double oral administration to puppies at a dose of 1.0 ml/5,0 kg BW, which corresponds to a dose of R-praziquantel 1.5 mg/kg, pyrantel pamoate 20.0 mg/kg and silybin 1.7 mg/kg for toxocariasis, hookworm infection, dipylidiosis, teniosis and mixed invasion was 100 %.
 
 Anthelmintic drug «Prazitel® Specialis suspension» for cats after double oral administration to kittens at a dose of 1.0 ml/kg BW, which corresponds to a dose of R-praziquantel 1.5 mg/kg, pyrantel pamoate 15.0 mg/kg and silybin 1.7 mg/kg provides complete exemption animals from helminths with toxocariasis, hookworm infection, dipylidiosis, teniosis and mixed invasion.
 
 Thus, the high therapeutic effectiveness of the anthelmintic drug «Prazitel® Specialis suspension» for dogs and cats in puppies and kittens with intestinal worm infection has been experimentally confirmed.

Comparative analyses on the chemical compostion, phytochemcimal and antioxidant properties of selected milled varieties (finger and pearl millet)

Purpose: Millet is a major food source in the arid and semi-arid parts of the world especially among people with low socio-economic status. It is a good source of energy, protein, minerals, dietary Fibre, fatty acid, amino acid (especially sulphur containing amino acid), phytochemicals and a good source of antioxidant.
 Methods: The millet varieties were obtained from the central market in Katsina state, Nigeria. The millet varieties (finger and pearl millet) were cleaned by washing in water, de-watered, sun dried, milled into flour and stored in sealed polythene bags. Standard method were used to determine the phytochemical, atomic absorption spectrometer, amino acid profile was determined spectrometically using a gas chromatography (GC), antioxidant property was measured by determination of free radical scavenging ability (DPPH,FRAP and ABTS) and data was analyzed by one way analysis of variance (ANOVA) using SPSS (16.0) software. The result obtained from studied millet varieties showed the fatty acid profile contain more than 70% unsaturated fatty acid. Amino acid profile showed the presence of essential amino acid of nutritional importance (especially the sulphur containing amino acids). 
 Results: The results obtained from the studied millet varieties showed a protein content level within the range of (10.09%-10.85%), fat content level between the range (2.76%-4.43%), carbohydrate, fat and ash content between the range (71.56% - 73.18%), (2.23% - 3.24%) and (0.86% - 1.94%) respectively. The mineral composition showed it contained mineral elements of health importance, such as; phosphorus, calcium, potassium, sodium and magnesium as well as other minor elements such as copper, manganese, zinc and iron. Phytochemical analyses showed the presence of plant chemical such as; tannin, terpenoid, alkaloid, cardiac glycoside, saponin, oxalate, phytate, flavonoids and total phenol. Antioxidant analyses showed they possess ability to serve as reducing agent hence a rich source of antioxidant of health importance.
 Unique contribution to theory, practice and policy: The study revealed a high nutritional quality and possible therapeutic effect of the studied millet varieties which are locally sourced and relatively cheaper source of food for a teeming population like ours.

STUDY OF THE EFFECT OF LOMUSTIN ON HER2-POSITIVE BREAST CANCER IN FVB/N HER-2 TRANSGENIC MICE

Because of the high risk of brain metastases from HER2-positive breast cancer, the study of the anticancer activity of drugs used to treat brain tumors, in particular lomustine, is of great importance. In the FVB/N Her-2 transgenic mice bearing HER2-positive breast cancer (BC HER2+), a single oral administration of lomustine at a dose of 50 mg/kg resulted in a significant tumor growth inhibition (up to 96 %, p<0.0001). The tumor growth index (TGI) expressed as a ratio between the areas under the kinetic curves of tumor growth in the study and control groups and amounted to 33 % (p<0.001) indicated the high activity of lomustine. However, the effect of lomustine on intramuscularly transplanted Ehrlich tumor was insignificant (tumor growth inhibition and tumor growth index were <39 % and 68 %, respectively). Lomustine administered orally at a single dose of 50 mg/kg 24 hours after intracranial transplantation of BC HER2+ increased the median survival time up to 30 days in FVB/N mice compared to 21 days in the control group mice (p<0.001). The high therapeutic effect of lomustine in HER2-positive breast cancer mice is likely can be explained by the biological characteristics of this tumor; therefore clinical trials of lomustine for HER2-positive tumors are needed.

Chemotherapy against piroplasmosis and anaplasmosis in cattle

It has been established that Teilercid is a specific medication in the treatment of cattle theileriosis. Two-time intramuscular injection of Teilercid in a dose of 1 ml per 20 kg of live weight with an interval of 48 hours in combination with symptomatic and pathogenic agents has a high therapeutic effect against cattle theileriosis. Babesan is established to have high therapeutic efficacy in babesiosis (Babesia bigemina) and cattle anaplasmosis (Anaplasma marginale) at a dose of 2.0 and 3.0 ml per 100 kg of live weight, respectively, injected intramuscularly in combination with symptomatic and pathogenic agents. Neozidinum M at a dose of 1 ml per 20 kg of live weight intramuscularly has the efficiency of 93-100% in the treatment of cattle babesiosis and theileriosis.

Assessment of Changes of the Distance from Liver Surface to Isocenter during Proton Beam Treatment for Liver Cancer

In proton beam therapy, although it is possible to obtain a high therapeutic effect while suppressing the influence on liver function by conducting concentrated irradiation on liver tumor, hepatic parenchyma and liver tumors irradiated by proton beam show atrophic changes after therapy. If atrophic changes occur in period of proton beam therapy, it may change dose distribution for liver tumor. We tried to evaluate the changes of size and shape of liver during proton beam treatment by the use of CT images. 18 consecutive cases (16 males and 2 females, from 56 to 84 years (median 69.5 years)) treated with proton beam therapy for liver cancer were included. 15 cases had hepatocellular carcinoma, 2 cases had metastatic liver cancer, a case had intrahepatic bile duct cancer, and 4 cases were treated with 66GyE in 10 fractions for two weeks, 8 cases with 76GyE in 20 fractions and 6 cases were treated with others (70-83.6GyE in 22-38 fractions.) The distances from the liver surface to the isocenter along the proton beam were measured on the CT images for radiation planning and compared with those measured on the CT images obtained on the day of the last irradiation. Total 42 beam directions of 18 cases were studied. In 13 beams, the distances increased by 0.4 to 4 mm, whereas, those were shortened by 0.4 to 9.5 mm in 24 beams. 5 beams had no changes of distances. 1 of 4 cases treated with 10 fractions, 2 of 8 cases with 20 fractions, and 1 of 6 cases with over 20 fractions showed the changes more than 5mm. The change of the distance from liver surface to isocenters occurred in period of proton beam therapy. Although a large part of changes were acceptable, some case showed the changes more than 5mm and these change may occur change dose distribution for liver tumor. It was suggested that it would be useful to evaluate the deformation of the liver during proton therapy and correct plans as necessary.

Using ultraviolet corneal crosslinking for the treatment of corneal ulcers and other corneal pathologies in animals

Purpose. To study the effects of corneal collagen cross-linking (CCL) using ultraviolet-A (UVA) irradiation with riboflavin on the eye’s anterior segment structures in corneal ulcers and other keratopathies in animals.Material and methods. The study involved 26 animals (39 eyes) — 10 cats, 10 dogs, and 6 horses with ulcers, corneal staphyloma, dry and autoimmune keratoconjunctivitis. Examination included slit-lamp biomicroscopy, ophthalmoscopy (in cases of transparent cornea), tear production test, and staining the eye surface with vital dyes. CCL was performed using UVA radiation of LEDs with a fiber optic output (wavelength 370 nm, radiation power 3 mW/cm2) combined with 0.1 % riboflavin instillation according to the protocol we developed, which specifies various numbers and durations depending on the diagnosis and therapeutic effect desired.Results. Restoration of the shape and transparency of the cornea, relief of anterior eye inflammation, and normalization of tear production occurred much sooner than using traditional treatment. The restoration of vision occurred 2 to 3 months earlier in eyes with corneal staphyloma; more than 4 to 5 months earlier in eyes with keratoconjunctivitis; no relapses were noted in eyes with ulcerative processes, and the restoration of the function of stratified squamous epithelium was achieved within 2 or 3 weeks.Conclusions. The inclusion of modified UFA-based CCL in the treatment scheme of corneal ulcers and staphylomas as well as dry and autoimmune keratoconjunctivitis enables a high therapeutic effect of anterior eye structure restoration. In future, the results obtained could serve as basis for using the developed technology in the treatment of similar eye pathologies in humans.

Implicit Attachment Schemas and Therapy Outcome for Panic Disorder Treated with Manualized Confrontation Therapy

Background: Different studies have shown that a patient’s attachment correlates with the psychotherapy outcome. However, these findings are based on the traditional interview and paper and pencil attachment methods. Latency-based methods like the Implicit Association Test (IAT) have not yet been investigated in clinical attachment research, specifically in therapy outcome research. Objectives: It can be hypothesized that patients with positive schemas of their mother and their partner may show a better psychotherapeutic outcome than those with less positive schemas of their mother/partner. Method: A sample of 103 patients suffering from panic disorder with or without agoraphobia (age 36.73, SD = 10.80), including 56% of patients with affective or other anxiety disorders as comorbidities without a personality disorder, based on the Structured Clinical Interview for DSM-IV (SCID-I/II), were treated with a manualized cognitive-behavioral confrontation therapy. Two IATs (for mother and partner) were implemented before the therapy (t1). The symptom reduction was assessed by the Symptom Checklist-90 (SCL-90) and the Beck Depression Inventory (BDI) with symptoms at t1 and IAT at t1 as predictors of symptoms at t2. Results: The results confirmed a moderate to high therapeutic effect of the confrontation therapy. Furthermore, the mother’s IAT at t1 predicted the Global Severity Index (β = 0.20) as well as the Anxiety subscale (β = 0.18) at t2 above and beyond the t1 measurement of the criteria. Conclusions: Implicit attitudes of the mother predicted the symptom reduction and a better therapeutic outcome. Relationship aspects with less impact awareness predicted the therapeutic outcome, even though mostly cognitive-behavioral techniques were used.

Tandem activated photodynamic and chemotherapy: Using pH-Sensitive nanosystems to realize different tumour distributions of photosensitizer/prodrug for amplified combination therapy

Photodynamic therapy (PDT) combined with hypoxia-activated prodrugs to overcome hypoxia environment has been recently explored as a promising clinical modality for cancer therapy. Nevertheless, delivering these two therapeutic agents together to different tumour areas that possess a number of biological barriers remains a considerable challenge. Herein, we used the semiconducting polyelectrolyte-based zwitterionic photosensitizer (PFNS) to modify the surface of upconversion nanoparticles (NPs) and prepare near-infrared (NIR) light-responsive PDT agents (UCNP@PFNS). A pH-sensitive Mn-Ca3(PO4)2 (MnCaP) layer was further coated onto UCNP@PFNS with the hypoxia-activated prodrug AQ4N incorporated inside. The final nanocomposites exhibited a diameter of 73 nm with high stability in the blood and a remarkably enhanced permeability and retention (EPR) effect in tumours. Importantly, when these nanoparticles reached the tumour site, the acidic tumour microenvironment (pH 6.5–6.8) decomposed the MnCaP layer, releasing both UCNP@PFNS (30 nm) and AQ4N. The relatively small size of UCNP@PFNS and AQ4N satisfied the different distribution requirements in tumour and achieved a high therapeutic effect, thereby reaching an inhibition rate of as high as 83%. In addition, Mn2+ ions can be released during the decomposition of CaP, leading to a significantly increased magnetic resonance (MR) signal in the tumour site. Overall, we report a nanoparticle guided by MRI and fluorescence imaging possesses of tandem active pattern of PDT and chemotherapy, which is promising for future clinical diagnosis and treatment.

Thermosensitive polysaccharide particles for pulmonary drug delivery

In the present study, we have prepared drug carriers for pulmonary administration: temperature-responsive polysaccharide particles prepared through an emulsion formation and a subsequent sol-gel transition of polysaccharides. The particles are obtained by the cooling of w/o (water-in-oil) emulsions prepared from an aqueous polysaccharide solution and a surfactant-dissolving organic solvent. We found that highly stable s/o (solid-in-oil) suspensions were formed regardless of HLB value, structure, and composition of the surfactants when high-molecular-weight surfactants were used. There are two possible important factors affecting the formation of spherical κ-carrageenan particles: (1) the formation of physically crosslinked domains inside the particle by means of the increase of concentrations of polysaccharides and cations and (2) the formation of a stable solid-liquid interfaces by using high-molecular-weight surfactants. We obtained stable polysaccharide particles with dimpled surfaces. As a result of the in vitro aerosol dispersion performance of the κ-carrageenan particles with the cascade impactor, we identified the characteristic delivery behavior of κ-carrageenan particles: the κ-carrageenan particles delivered more to the alveoli than to the pharynx and bronchi, despite their high density. The present study shows that the “dimpled” κ-carrageenan particles can likely stay in the alveoli so that high therapeutic effects will likely occur in pulmonary administration.

Familial Hypercholesterolemia and Lipoprotein Apheresis.

Lipoprotein apheresis has been developed as the treatment for refractory familial hypercholesterolemia (FH) to remove low-density lipoprotein (LDL), which is the main pathogenic factor. Currently, three procedures are available in Japan, including the plasma exchange, double-membrane filtration, and selective LDL adsorption. Selective LDL adsorption, which was developed in Japan, has been one of the most common treatment methods in the world. Lipoprotein apheresis enabled the prevention of atherosclerosis progression even in homozygous FH (HoFH) patients. However, in our observational study, HoFH patients who started lipoprotein apheresis in adulthood had a poorer prognosis than those who started in childhood. Therefore, HoFH patients need to start lipoprotein apheresis as early as possible. Although the indication for lipoprotein apheresis in heterozygous FH (HeFH) patients has been decreasing with the advent of strong statins, our observational study showed that HeFH patients who discontinued lipoprotein apheresis had a poorer prognosis than patients who continued apheresis therapy. These results suggest that it is beneficial for very-high-risk HeFH patients to be treated by lipoprotein apheresis even if their LDL cholesterol is controlled well by lipid-lowering agents. Since launching a new class of lipid-lowering agents, proprotein convertase subtilisin/kexin type 9 (PCSK9) antibody and microsome triglyceride transfer protein inhibitors, the indication for lipoprotein apheresis in FH has been changing. However, despite the development of these drugs, lipoprotein apheresis is still an option with a high therapeutic effect for FH patients with severe atherosclerotic cardiovascular disease.

The clinical efficacy of treatment using the autologous non-cultured epidermal cell suspension technique for stable vitiligo in 41 patients

Background: Vitiligo is an acquired depigmentation skin disorder mainly caused by the destruction of melanocytes. There are many therapeutic options available for vitiligo, but the options are not uniformly effective.Objectives: This study aimed to explore the clinical effect of the autologous non-cultured epidermal cell suspension (NCES) technique in the treatment of patients with stable vitiligo.Methods: A retrospective study of before-after comparisons was undertaken with 41 patients with stable vitiligo who received treatment with the NCES technique. The percentage of repigmentation area was evaluated using image analysis of the appearance before and 6–9 months after operation.Results: A total of 41 patients (18 males and 23 females) with a duration of clinical stability for ranging from 1 to 10 years (mean 1.6 ± 1.9) were included. The mean age was 20.2 years (range, 8–50) and 4 (9.8%) were children under the age of 14 years. After 6–9 months of follow-up, 80.5% (33/41) of the patients showed good response; among these patients, 17.1% (7/41) showed complete or almost complete repigmentation. Interestingly, all 4 children showed very good response (more than 76% repigmentation). There were no significant differences in the efficacy of treatment between the different transplantation areas of the facial neck, trunk, and distal limbs and there were no adverse effects such as infection or scar formation.Limitation: This study included only a single center with a small sample size.Conclusions: Our study shows that the NCES technique has a high therapeutic effect, is safe for patients with stable vitiligo, and may be a very promising potential option for treating children.

PENINGKATAN DISOLUSI ROSUVASTATIN CALSIUM DARI SEDIAAN TABLET DENGAN TEKNIK LIQUISOLID DAN PEMBENTUKAN KOMPLEKS INKLUSI

Rosuvastatin calcium is a salt form of rosuvastatin with antilipidemia activity. Rosuvastatin Calcium classified in class two of Biopharmaceutics Clasification System (BCS) has low solubility in water (17.96 mg / L) and high permeability. Based on this, rosuvastatin calcium needs to be formulated appropriately in order to produce high bioavailability and maximum therapeutic effect. The bioavailability of BCS 2 drug is determined by the dissolution rate of the drug in gastrointestinal fluid so that a technique is needed in formulating the drug. This study aims to develop a formulation technique for rosuvastatin calcium tablets through liquisolid technique and formation of inclusion complexes with β-cyclodextrin in order to increase the rate of dissolution. Tablet formulation with liquisolid technique was made with a concentration of 10% rosuvastatin calcium in propylene glycol, with a ratio of US2® (carrier) and Aerosil 200 (coating) made with a ratio of 10: 1 and 20: 1. In addition to the formulation with liquisolid technique, formulations were also carried out with the complex inclusion technique of rosuvastatin calcium-β-cyclodextrin using kneading method and freeze drying method with a mol ratio of 1: 1 and 1: 2. The liquisolid system and inclusion complexes formed were characterized using FTIR and SEM. Characterization results indicated changes in the form of polymorphous rosuvastatin calcium. Tablet formulations were made by direct compression using a liquisolid system and an inclusion complex equivalent to 10 mg of rosuvastatin calcium. Based on the results of the ANOVA statistical test and further LSD tests showed that calcium rosuvastatin tablets made with liquisolid and inclusion complexes can increase the dissolution rate compared to pure rosuvastatin calcium tablets and inovator rosuvastatin calcium tablets. The highest dissolution rate was produced by liquisolid R20: 1 tablet at 60 minutes at 85.53 ± 1.02% in an enzyme-free simulated gastric fluid dissolution medium and 110.02 ± 1.71% in an enzyme-free simulated intestinal fluid dissolution medium.

СОВРЕМЕННЫЙ ВЗГЛЯД НА АНТИБАКТЕРИАЛЬНУЮ ОБРАБОТКУ КОРНЕВОГО КАНАЛА С ПОМОЩЬЮ ЛАЗЕРНОЙ ФОТОДИНАМИЧЕСКОЙ ТЕРАПИИ

Importance. Currently, endodontic dental treatment is a complex manual process that requires in-depth knowledge of the anatomy of the crown and root part of the tooth, all this is necessary, as is a three-dimensional assessment of the structure of the pulp chamber of the root canal system, using modern technologies. In other words, a favorable result of endodontic treatment can be achieved in case of correct formation of access to the root canals and the qualitative removal of any inflamed, infected, degeneratively altered and necrotized pulp tissues.
 Objectives ― the study of the antibacterial effect and the possibility of using a laser photodynamic system for antibacterial treatment of root canals containing fragments of endodontic instruments.
 Methods. Fifteen patients aged from 18 to 50 years with 20 root canals containing fragments of an endodontic instrument were selected for work, previously treated for chronic periodontitis. Three samples for microbiological examination were taken: before the start of treatment, the sampling of dentinal chips from the root canal with a sterile file (sample A), after the instrumental treatment, medical treatment with 2.25 % sodium hypochlorite solution and the sampling of dentinal chips from the channel wall (sample B). Further, a photosensitase solution was placed in the root canal for 60 sec., Exposure was carried out with a laser beam for 120 seconds (HELBO system, Austria), dentinal chips collected (Sample C).
 Results. In samples A, the infection level corresponded to 4 points (marked bacterial load); in samples B ― 2 (average); in samples C ― 0. 
 Conclusions. The use of a laser photodynamic system in the root canals, provides a high therapeutic effect, accelerates the process of medical treatment of the canal canal, by removing the dentinal chips and smear layer.

Cisplatin-loaded polymeric complex micelles with a modulated drug/copolymer ratio for improved in vivo performance

This study aimed to evaluate the performance of cisplatin-loaded polymeric micelles (CDDP-PMs) with different drug/copolymer ratios of 1:1, 1:3 and 1:6 (w/w) prepared by coordinated complexation and self-assembly method. The mass ratio influenced the self-assembly behaviors and the complex degree, where both single- and double- complexation existed in CDDP-PMs. With the increase of CDDP/copolymer ratio, the particle size and drug loading increased, while encapsulation efficiency decreased. The PEG density of CDDP-PM1-6, CDDP-PM1-3 and CDDP-PM1-1 were 0.20, 0.61 and 0.38 PEG/nm2, respectively. CDDP-PM1-3 and CDDP-PM1-6 had similar sustained release behavior, while CDDP-PM1-1 showed burst release. Pharmacokinetics showed the AUC of CDDP-PM1-6, CDDP-PM1-3 and CDDP-PM1-1 was 27.2, 76.6 and 13.0 fold higher than CDDP solution. Tissue distribution presented the platinum concentration of CDDP-PM1-6, CDDP-PM1-3 and CDDP-PM1-1 was 1.03, 0.80 and 0.48 times of CDDP solution in kidney at 10 min, and 17.61, 28.63 and 16.6 times in tumor at 48 h respectively, indicating CDDP-PMs significantly reduced nephrotoxicity and increased tumor-targeting accumulation. In vivo antitumor test showed that CDDP-PMs exhibited an improved antitumor efficacy and lower systemic toxicity compared with CDDP solution. From CDDP-PM1-1 to CDDP-PM1-6, the toxicity decreased with the increase of copolymer ratio, but the tumor inhibition rate also decreased. CDDP-PM1-3 had relative high therapeutic effect and low toxicity compared with other formulations. CDDP-PM1-3 could improve the antitumor efficacy by increasing the dose within systemic tolerability, but CDDP solution cannot. This work provides an effective strategy by modulating drug/copolymer ratio of CDDP-PMs to balance the antitumor efficacy and toxicity for better payoff. Statement of SignificanceCancer chemotherapy always exists a contradiction between antitumor efficacy and toxicity. Higher efficacy against tumor often associated with larger toxicity for normal tissues. This work provides an important strategy by modulating the drug/copolymer ratios to balance the antitumor efficacy and toxicity to obtain better payoff. The cisplatin-loaded polymeric micelles (CDDP-PMs) based on the complexation between CDDP and copolymer with different mass ratios make differences in vitro and in vivo because of the single- or double-complexation degree. Most importantly, we found the balance at CDDP/copolymer ratio of 1:3, which has relative high therapeutic effect and low toxicity compared with other formulations. CDDP-PM1-3 could improve the antitumor efficacy by increasing the dose within systemic tolerability, but CDDP solution cannot.