[(TREATMENT FOR CUTANEOUS LEISHMANIASIS: HISTORICAL ASPECTS)].

The paper presents an overview of treatment for cutaneous leishmaniasis from ancient times to the >iesent day. Tradi- tional healers had an arsenal of remedies and various treatment regimens for cutaneous leishmaniasis, which showed varying effectiveness and different outcome and have found scientific rationale and used in practical medicine in modem times. The problem with of a lack of etiotropic drugs to treat patients with cutaneous leishmaniasis in the national healthcare is indicated.

[The influence of sinusoidal modulated currents on the fatty acid composition of plasma and blood erythrocytes in the patients presenting with chronic cholecystitis]. / Vliyanie sinusoidal'nykh modulirovannykh tokov na sostav zhirnykh kislot plazmy i eritrotsitov krovi u patsientov s khronicheskim kholetsistitom.

The objective of the present study was to evaluate the effectiveness of the treatment with sinusoidal modulated currents on lipid metabolism in the patients presenting with chronic cholecystitis in the state of remission. PATIENTS AND METHODS: The study included 25 patients with chronic non-calculosis cholecystitis in phase of remission and 20 healthy subjects (controls). We studied the serum lipid spectrum as well as the fatty acid composition of plasma and blood erythrocytes before and after therapy with sinusoidal modulated currents applied to the right-sided hypochondrium region. RESULTS AND DISCUSSION: The treatment of the patients with chronic cholecystitis in remission with the use of sinusoidal modulated currents produced moderate lipid-modulatory and membranotropic effects mediated through the activation of the processes of lipid metabolism that may result in the depletion of the pool of essential polyunsaturated fatty acids. CONCLUSION: The results of this study give evidence that it is advisable to treat the patients presenting with chronic cholecystitis by sinusoidal modulated currents in the combination with the oral intake of exogenous polyunsaturated fatty acids.

[Blood fatty acids in the development and correction of metabolic syndrome]. / Zhirnye kisloty krovi v formirovanii i korrektsii metabolicheskogo sindroma.

AIM: to investigate the composition of plasma fatty acids (FA) and red blood cells and the level of eicosanoids in patients with metabolic syndrome (MS) and to assess whether metabolic disturbances may be corrected during a cycle use of an ω-3 polyunsaturated fatty acid (PUFA). SUBJECTS AND METHODS: Examinations were made in 46 patients, including Group 1 (a control group) of 15 persons without MS components; Group 2 of 31 patients with MS, Group 3 of 16 MS patients who had taken an ω-3 PUFA for 6 months, and Group 4 of 15 MS patients who had received the drug for 12 months. The composition of plasma FA and red blood cells was analyzed on a gas-liquid chromatograph. An enzyme immunoassay was used to measure the serum levels of tumor necrosis factor-α (TNF-α) and eicosanoids (thromboxane B2, 6-keto-prostaglandin F1α, leukotriene B4). A biologically active additive from the king crab (Paralithodes camtschatica) hepatopancreas was used as a source of ω-3 PUFA. RESULTS: Having a higher proportion of linoleic and α-linolenic acids in the plasma, the patients were found to have decreased levels of ω-3 and ω-6 PUFAs (linoleic and α-linolenic, arachidonic, and eicosapentaenoic acids) and a larger proportion of Mead acid and saturated FAs (myristic and stearic acids) in the red blood cells, suggesting that that cellular blood FA transfer was impaired and FAs were absorbed by cells. Their serum samples showed the high levels of leukotriene B4, 6-keto-prostaglandin F1α, and thromboxane A2. The long-term (6- and 12-month) use of ω-3 PUFA from the king crab hepatopancreas had a positive impact in modifying the lipid FA composition of red blood cells and in eliminating deficiencies of physiologically important ω-3 and ω-6 PUFAs in the blood cells. CONCLUSION: The findings suggest that FAs and their metabolites play an important role in the pathogenesis of MS and that dietary ω-3 PUFA should be incorporated into a package of preventive and therapeutic measures for MS.

Hormetic effect induced by depleted uranium in zebrafish embryos.

The present work studied the hormetic effect induced by uranium (U) in embryos of zebrafish (Danio rerio) using apoptosis as the biological endpoint. Hormetic effect is characterized by biphasic dose-response relationships showing a low-dose stimulation and a high-dose inhibition. Embryos were dechorionated at 4h post fertilization (hpf), and were then exposed to 10 or 100µg/l depleted uranium (DU) in uranyl acetate solutions from 5 to 6 hpf. For exposures to 10µg/l DU, the amounts of apoptotic signals in the embryos were significantly increased at 20 hpf but were significantly decreased at 24 hpf, which demonstrated the presence of U-induced hormesis. For exposures to 100µg/l DU, the amounts of apoptotic signals in the embryos were significantly increased at 20, 24 and 30 hpf. Hormetic effect was not shown but its occurrence between 30 and 48 hpf could not be ruled out. In conclusion, hormetic effect could be induced in zebrafish embryos in a concentration- and time-dependent manner.

Combined effects of depleted uranium and ionising radiation on zebrafish embryos.

In the environment, living organisms are exposed to a mixture of stressors, and the combined effects are deemed as multiple stressor effects. In the present work, the authors studied the multiple stressor effect in embryos of the zebrafish (Danio rerio) from simultaneous exposure to alpha particles and depleted uranium (DU) through quantification of apoptotic signals at 24 h post-fertilisation (hpf) revealed by vital dye acridine orange staining. In each set of experiments, dechorionated zebrafish embryos were divided into 4 groups, each having 10 embryos: Group (C) in which the embryos did not receive any further treatment; Group (IU) in which the embryos received an alpha-particle dose of 0.44 mGy at 5 hpf and were then exposed to 100 µg l(-1) of DU from 5 to 6 hpf; Group (I) in which the embryos received an alpha-particle dose of 0.44 mGy at 5 hpf and Group (U) in which the dechorionated embryos were exposed to 100 µg l(-1) of DU from 5 to 6 hpf. The authors confirmed that an alpha-particle dose of 0.44 mGy and a DU exposure for 1 h separately led to hormetic and toxic effects assessed by counting apoptotic signals, respectively, in the zebrafish. Interestingly, the combined exposure led to an effect more toxic than that caused by the DU exposure alone, so effectively DU changed the beneficial effect (hormesis) brought about by alpha-particle irradiation into an apparently toxic effect. This could be explained in terms of the promotion of early death of cells predisposed to spontaneous transformation by the small alpha-particle dose (i.e. hormetic effect) and the postponement of cell death upon DU exposure.

[FEATURES OF OTOGENIC INTRACRANIAL COMPLICATIONS AT THE PRESENT STAGE].

A retrospective analysis of treatment was made in 127 adult patients with acute and chronic otitis media complicated by suppurative-inflammatory pathology of the brain. Purulent meningitis was revealed in 52 (40.9%) of hospitalized patients. Meningoencephalitis was often diagnosed in the cases of acute otitis media (15.4%) and in cases of chronic otitis (22.7%). The otogenic brain abscess was detected in 13.5% of otitis media cases and it was noted to be twice frequent (33.3%) in cases of purulent otitis media. The patients 124 (97.6%) have been operated. An extended mastoidotomy and antromastoidotomy were performed in the acute purulent otitis media. An extended radical operation on the ear was applied in case of chronic otitis media. Performance of craniotomy and complete removal of the abscess using modern systems of neuronavigation showed a higher clinical efficacy as compared with transtemporal approach during sanitizing intervention on the ear including the opening and abscess drainage in surgery of otogenic abscesses of the brain.

Inhibition of FASN reduces the synthesis of medium-chain fatty acids in goat mammary gland.

Fatty acid synthase (FASN) is known as a crucial enzyme of cellular de novo fatty acid synthesis in mammary gland which has been proved as the main source of short and medium-chain fatty acids of milk. However, the regulatory role of FASN in goat-specific milk fatty acids composition remains unclear. We cloned and analyzed the full-length of FASN gene from the mammary gland of Capra hircus (Xinong Saanen dairy goat) (DQ 915966). Comparative gene expression analysis suggested that FASN is predominantly expressed in fat, small intestine and mammary gland tissues, and expresses higher level at lactation period. Inhibition of FASN activity by different concentrations (0, 5, 15, 25 and 35 µM) of orlistat, a natural inhibitor of FASN, resulted in decreased expression of acetyl-CoA carboxylase α (ACCα), lipoprotein lipase and heart-type fatty acid binding protein (H-FABP) in a concentration-dependent manner in goat mammary gland epithelial cells (GMEC). Similar results were also obtained by silencing of FASN. Additionally, reduction of FASN expression also led to apparent decline of the relative content of decanoic acid (C10:0) and lauric acid (C12:0) in GMEC. Our study provides a direct evidence for inhibition of FASN reduces cellular medium-chain fatty acids synthesis in GMEC.

An unblinded, randomised phase II study of platinum-based chemotherapy with vitamin B12 and folic acid supplementation in the treatment of lung cancer with plasma homocysteine blood levels as a biomarker of severe neutropenic toxicity.

BACKGROUND: Vitamin B12 and folic acid (referred to as vitamin supplementation) improves the toxicity profile of pemetrexed containing regimens. Low baseline vitamin B12 and folate levels are reflected in a raised total homocysteine level (HC). Studies have suggested that pretreatment HC levels predict neutropenia toxicity. We have tested supplementation with vitamin B12 and folate in non-pemetrexed platinum-based regimens to decrease treatment-related toxicity and looked for a correlation between toxicity and change in homocysteine levels. PATIENT AND METHOD: Eighty-three patients with advanced lung cancer and malignant mesothelioma were randomly assigned to receive platinum-based chemotherapy with (arm A) or without (arm B) vitamin B12 and folic acid supplementation. The primary end point was grade 3/4 neutropenia and death within 30 days of treatment. Secondary end points included quality of life, overall survival (OS) and the relationship between baseline and post supplementation HC levels and toxicity. RESULTS: In the intention-to-treat population, no significant difference was seen between the two groups with respect to chemotherapy-induced grade 3/4 neutropenia and death within 30 days of chemotherapy (36% vs 37%; p=0.966, emesis (2% vs 6%; p=0.9) or OS (12.3 months vs 7 months; p=0.41). There was no significant difference in survival rates by baseline HC level (p=0.9). Decrease in HC with vitamin supplementation was less frequent than expected. High baseline HC levels decreased with vitamin supplementation in only 9/36 (25%) patients (successful supplementation). Post hoc analysis showed that patients in arm A who were successfully supplemented (9/36=25%) had less neutropenic toxicity (0% vs 69%; p=0.02) compared to unsupplemented patients. CONCLUSIONS: The addition of vitamin B12 and folic acid to platinum-containing regimens did not overall improve the toxicity, quality of life or OS. Rates of grade 3/4 neutropenia at 36/37% was as predicted. Further studies to increase the rate of successful supplementation and to further test the biomarker potential of post supplementation HC levels in predicting chemotherapy-induced neutropenia in platinum-based chemotherapy are warranted. TRIAL REGISTRATION NUMBER: EudracCT 2005-002736-10 ISRCTN8734355.

A phase II study of gemcitabine and cisplatin plus sorafenib in patients with advanced biliary adenocarcinomas.

BACKGROUND: This study evaluated the addition of sorafenib to gemcitabine and cisplatin in biliary adenocarcinoma first-line therapy. METHODS: Patients with advanced biliary adenocarcinomas received gemcitabine 1000 mg m(-2) and cisplatin 25 mg m(-2) on a 2 weeks on/1 week off cycle and sorafenib 400 mg twice daily. After the initial 16 patients were enrolled, the chemotherapy doses were amended in view of grade 3 and 4 hand-foot skin reaction and haematologic toxicity. Subsequently, 21 patients received gemcitabine 800 mg m(-2), cisplatin 20 mg m(-2) and sorafenib 400 mg. The primary end point was an improvement in 6-month progression-free survival (PFS6) from historical 57-77% (90% power, type I error of 10%). Pretreatment pERK, evaluated by immunostaining, was correlated with clinical outcome. RESULTS: A total of 39 patients were accrued. The most common grade 3-4 toxicities noted in >10% of patients were fatigue, elevated liver function tests and haematologic toxicities including thromboemboli, hyponatraemia and hypophosphataemia. Six-month progression-free survival was 51% (95% confidence interval (CI) 34-66%). Median PFS and overall survival were 6.5 (95% CI: 3.5-8.3) and 14.4 months (95% CI: 11.6-19.2 months), respectively. No correlation was observed between pERK and outcomes. CONCLUSION: The addition of sorafenib to gemcitabine and cisplatin in biliary adenocarcinomas did not improve efficacy over historical data, and toxicity was increased.

Bystander effect between zebrafish embryos in vivo induced by high-dose X-rays.

We employed embryos of the zebrafish, Danio rerio, for our studies on the in vivo bystander effect between embryos irradiated with high-dose X-rays and naive unirradiated embryos. The effects on the naive whole embryos were studied through quantification of apoptotic signals at 25 h post fertilization (hpf) through the terminal dUTP transferase-mediated nick end-labeling (TUNEL) assay followed by counting the stained cells under a microscope. We report data showing that embryos at 5 hpf subjected to a 4-Gy X-ray irradiation could release a stress signal into the medium, which could induce a bystander effect in partnered naive embryos sharing the same medium. We further demonstrated that this bystander effect (induced through partnering) could be successfully suppressed through the addition of the nitric oxide (NO) scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) into the medium but not through the addition of the CO liberator tricarbonylchloro(glycinato)ruthenium(II) (CORM-3). This shows that NO was involved in the bystander response between zebrafish embryos induced through X-ray irradiation. We also report data showing that the bystander effect could be successfully induced in naive embryos by introducing them into the irradiated embryo conditioned medium (IECM) alone, i.e., without partnering with the irradiated embryos. The IECM was harvested from the medium that had conditioned the zebrafish embryos irradiated at 5 hpf with 4-Gy X-ray until the irradiated embryos developed into 29 hpf. NO released from the irradiated embryos was unlikely to be involved in the bystander effect induced through the IECM because of the short life of NO. We further revealed that this bystander effect (induced through IECM) was rapidly abolished through diluting the IECM by a factor of 2× or greater, which agreed with the proposal that the bystander effect was an on/off response with a threshold.

The 3Ns chromosome of Psathyrostachys huashanica carries the gene(s) underlying wheat stripe rust resistance.

Stripe rust (Puccinia striiformis tritici (Pst)) is one of the most destructive diseases of wheat in the world. Exploiting and utilizing stripe rust resistance genes of wild species has become an essential strategy for resistance breeding. Psathyrostachyshuashanica Keng ex Kuo is a wild species in Triticeae that has been used for wheat improvement because of its high resistance or immunity to stripe rust. In this study, 9 wheat-P. huashanica addition lines were characterized by Giemsa C-banding, genomic in situ hybridization (GISH), and disease resistance evaluation. Giemsa C-banding and GISH demonstrated that lines 163-5, 165-1, 183-5, 240-3, and 240-4 are P. huashanica 3Ns chromosome monosomic addition lines; lines 183-1 and 183-20 are P. huashanica 3Ns chromosome disomic addition lines; line 165-20 is a P. huashanica 3Ns and 4Ns chromosomes double disomic addition line, and line 219-1 is a P. huashanica 1Ns and 3Ns/5A chromosomes double disomic addition-substitution line. All these addition lines with P. huashanica 3Ns chromosome(s) expressed high resistance or immunity to stripe rust. By comparing the series of wheat-P. huashanica chromosome addition lines, we concluded that the P. huashanica 3Ns chromosome carries the gene(s) for resistance or immunity to stripe rust. These addition lines can be used as a donor source of novel stripe rust resistance to wheat breeding programs.

Randomized clinical trial of intravenous soybean oil alone versus soybean oil plus fish oil emulsion after gastrointestinal cancer surgery.

BACKGROUND: Specific immunonutrients may reduce the incidence of postoperative complications and shorten recovery time. This randomized trial evaluated the clinical efficacy of a fish oil emulsion on outcome and immune function after gastrointestinal cancer surgery. METHODS: A total of 206 patients with gastrointestinal or colonic cancer were randomized to receive isocaloric and isonitrogenous intravenous infusions of either soybean oil alone (1.2 g per kg bodyweight per day; control group, 103 analysed) or soybean plus fish oil emulsion (1.0 and 0.2 g per kg per day respectively; treatment group, 100 analysed) over 20-24 h daily for 7 days after surgery. RESULTS: Baseline data were comparable in the two groups. There were fewer infectious complications (four versus 12 on day 8; P = 0.066), systemic inflammatory response syndrome (SIRS) was significantly less common (four versus 13; P = 0.039) and hospital stay was significantly shorter (mean(s.d.) 15(5) versus 17(8) days; P = 0.041) in the treatment group. Total postoperative medical costs were comparable in the two groups (mean(s.d.) US $ 1269(254) and 1302(324) in treatment and control groups respectively; P = 0.424). The median (interquartile range) difference in CD4/CD8 between days 1 and 8 after surgery was + 0.30 (0.06 to 0.79) in patients receiving fish oil and + 0.20 (-0.19 to 0.55) in controls (P = 0.021). No severe adverse events occurred in either group. CONCLUSION: Fish oil emulsion-supplemented parenteral nutrition significantly reduced SIRS and length of hospital stay. These clinical benefits may be related to normalization of cellular immune functions and modulation of the inflammatory response.

Vestibular influences on postural instability induced by movements of the visual environment and support.

Subjects were maintained in a vertical posture standing on a hard support with a limited degree of freedom in the frontal plane. The stability of the vertical posture was assessed on the basis of the standard deviations (sigma) from the mean amplitude of head oscillations (in the frontal and sagittal planes) relative to the origin of the coordinate system. Sinusoidal rotations of the optokinetic cylinder in which subjects stood, sinusoidal rotations of the support, and combination of these rotations, with phase discordance between movements of the cylinder and the support, led to increases in sigma in all subjects. Feedback via the vestibular input was created using transmastoid galvanic vestibular stimulation. Changes in the feedback current showed a linear function relating to the amplitude and speed of head movement. Introduction of variations in the feedback function could be used to decrease sigma for lateral oscillations; increases (compared with values on calm standing in the dark) resulted from the use of any of the destabilizing treatments. Changes in sigma for oscillations in the sagittal plane were not systematic.

Production of eleutherosides in in vitro regenerated embryos and plantlets of Eleutherococcus chiisanensis.

High frequency somatic embryogenesis of Eleutheorcoccus chiisanensis was achieved through suspension culture of embryogenic cells in hormone-free Murashige and Skoog liquid medium supplemented with 30 g sucrose l-1. Cotyledonary somatic embryos were germinated and converted into plantlets using 20 microM: gibberellic acid which were then grown in a 10 l airlift bioreactor. HPLC analysis revealed the accumulation of eleutheroside B, E and E1 in the embryos and plantlets. Thus mass production of embryos and plantlets of E. chiisanensis can be achieved in liquid cultures and the biomass produced may become an alternative source of eleutherosides.

Protection by a taurine supplemented diet from lead-induced deficits of long-term potentiation/depotentiation in dentate gyrus of rats in vivo.

Previous studies have demonstrated that synaptic plasticity, which includes long-term potentiation (LTP) and depotentiation (DP) in hippocampus, is important for learning and memory. The purpose of this study is to evaluate the effect of taurine via drinking water on the lead-induced impairments of LTP and DP in rat dentate gyrus (DG) in vivo. The experiments were carried out in four groups of rats (control, lead-exposed, control and lead-exposed with a taurine-supplement diet, respectively). The input-output (I/O) function, excitatory postsynaptic potential (EPSP) and population spike (PS) amplitude were measured in the DG area of adult rats (60-90 days) in response to stimulation applied to the lateral perforant path. The results show that: 1. chronic lead exposure impaired LTP/DP measured on both EPSP slope and PS amplitude in DG area of the hippocampus; 2. in control rats, taurine had no effect on LTP/DP; 3. the amplitudes of LTP/DP of lead-exposed group were significantly increased by applying taurine. These results suggest that dietary taurine supplement could protect rats from the lead-induced impairments of synaptic plasticity and might be a preventive medicine to cure the cognitive deficits induced by lead.

San-Huang-Xie-Xin-Tang attenuates inflammatory responses in lipopolysaccharide-exposed rat lungs.

In this study, the potential anti-inflammatory effect of San-Huang-Xie-Xin-Tang (SHXT) and its main component baicalin on LPS-induced lung injury were investigated and compared to the profile of dexamethasone (DEXA) in a pre-clinical animal model. Post-treatment with SHXT (75 mg/kg), baicalin (1.5 mg/kg) and DEXA (0.5 mg/kg), significantly inhibited LPS-induced hypotension, lung edema and acute survival rates. Western blotting analysis results indicated that all of them significantly inhibited LPS-induced iNOS, TGF-beta, p38MAPK, and ICAM-1 expressions in the lung tissues. Results from ELISA analysis showed that SHXT, baicalin and DEXA all decreased plasma levels of IL-1beta, TNF-alpha, and MCP-1 caused by LPS. Based on these findings, SHXT and baicalin decreased plasma concentrations of IL-1beta, TNF-alpha, MCP-1, and expressions of TGF-beta, ICAM-1, phosphorylated p38 MAPK, and iNOS, which were associated with lung injury and lethality. These evidences indicated that SHXT and baicalin showed strong anti-inflammatory activity, similar to that observed for DEXA, and therefore implicated that herbal SHXT might be therapeutically useful for the treatment of endotoxic lung injury.

Methyl jasmonate elicitation enhanced synthesis of ginsenoside by cell suspension cultures of Panax ginseng in 5-l balloon type bubble bioreactors.

The effects of methyl jasmonate (MJ) elicitation on the cell growth and accumulation of ginsenoside in 5-l bioreactor suspension cultures of Panax ginseng were investigated. Ginsenoside accumulation was enhanced by elicitation by MJ (in the range 50-400 microM); however, fresh weight, dry weight and growth ratio of the cells was strongly inhibited by increasing MJ concentration. The highest ginsenoside yield was obtained at 200 microM MJ. In the second experiment, 200 microM MJ was added on day 15 during the cultivation. The ginsenoside, Rb group, and Rg group ginsenoside content increased 2.9, 3.7, and 1.6 times, respectively, after 8 days of MJ treatment. Rb group gisnsenosides accumulated more than Rg group ginsenosides. Among Rb group ginsenosides, Rb1 content increased significantly by four times but the contents of Rb2, Rc and Rd increased only slightly. Among Rg group ginsenosides, Rg1 and Re showed 2.3-fold and 3.0-fold increments, respectively, whereas there was only a slight increment in Rf group ginsenosides. These results suggest that MJ elicitation is beneficial for ginsenoside production using 5-l bioreactor cell suspension cultures.

Pharmacological activities of stromata of Cordyceps scarabaecola.

The chemical components of freeze-dried stromata from Cordyceps scarabaecola were examined. The stromata consisted of crude carbohydrates (55.1%) and crude proteins (14.2%). The stromata were also composed of a low content of crude ash (6.6%) and fat (1.5%). The composition of the carbohydrate in the stromata included a large quantity of glucose (46.6%), mannose (35.4%) and galactose (18.0%). The acidic amino acids such as glutamic acid (32.1 mg/g) and aspartic acid (24.7 mg/g) were present in a large quantity. The extracts of stromata did not reveal any inhibitory activity for AChE in vitro. It was observed that a hot-water extract (HW) of the stromata contributed significantly to the anticoagulant activity (60 s coagulating time) and anticomplementary activity (62% of ITCH50 value). The MeOH-soluble fraction (M) from the freeze-dried stromata inhibited TPA-induced O2- generation as effectively as the positive control, genistine 27%. The hot-water extract (HW) showed the most potent intestinal immune system modulation activity and the MeOH-soluble fraction (M) had intermediate activity.

Anti-stress and anti-fatigue effect of fermented rice bran.

The anti-stress and anti-fatigue effects of a hot water extract of fermented rice bran (FRB) were investigated with Saccharomyces cerevisae IFO 2346 on rats or mice. Oral administration (1 g/kg/day) of a hot water extract of FRB inhibited major changes in weight of the adrenal, thymus, spleen and thyroid, showing the anti-stress effect. A hot water extract of FRB also inhibited the increase of GPT and LDH activity, cholesterol and serum glucose levels. Administration (1 g/kg/day) for 2 weeks significantly prolonged the swimming time, resulting in an increase of the anti-fatigue effect. From these results, it can be considered that FRB has an anti-stress and anti-fatigue effect.