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Copyright of Farmacist.ro is the property of MEDICHUB MEDIA, S.R.L. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Poly(vinyl alcohol)/hyaluronic acid cryogels loaded with methotrexate were studied. The physical-chemical characterization of cryogels was performed by FT-IR spectroscopy, scanning electron microscopy, differential scanning calorimetry and dynamic mechanical thermal analysis. Acute toxicity and haematological parameters were determined by "in vivo" tests. The biocompatibility tests proved that the obtained cryogels showed significantly decreased toxicity and are biocompatible. The pH-responsiveness of the swelling behaviour and of the methotrexate release from the poly(vinyl alcohol)/hyaluronic acid (PVA/HA) cryogels were studied in a pH interval of 2-7.4. A significant change in properties was found at pH 5.5 specific for treatment of affected skin in psoriasis disease. [ABSTRACT FROM AUTHOR]

During time, due to its antimicrobial effects, phytotoxic properties, antioxidant potential and insecticidal activities Pinus brutia have been largely used in alternative medicine. The aim of our study was the experimental investigation on the effects of a P. brutia extract on spontaneous behavior in rats. Material and methods: The experiment was carried out on white Wistar rats, distributed in 4 group of 6 animals each, treated intraperitoneally as follows: group 1 (coded M): saline solution 0.1 ml/100 g weight; group 2 (coded MgCl2): magnesium chloride 1 mmol/kbw; group 3 (coded PB-1): P. brutia extract 112.5 mg/kbw; group 4 (coded PB-2): P. brutia extract 56.25 mg/kbw. Locomotor activity and exploratory behavior of the animals were evaluated using the LE-8811 Actimeter PanLAB device, in order to determine the number of horizontal, vertical and stereotype movements. The data were presented as mean +/- standard deviation and analyzed using SPSS program for Windows version 17.0 and ANOVA method. Brain fragments were harvested for histopathological evaluation. Results: Intraperitoneal administration of 112.5 mg/kbw, but not of 56.25 mg/kbw of P. brutia extract was associated with a reduction of rat horizontal and vertical movements, statistically significant compared to control group, in this behavioral experimental model. Both extracts from P. brutia did not considerable influence the animal stereotype movements. The extract determined no histopathological variations compared to the control group. Conclusion: The treatment with P. brutia extract (112.5 mg/kbw) resulted in significant decrease of spontaneous motor activity in Actimeter test in rats. [ABSTRACT FROM AUTHOR]

A rapid and sensitive liquid chromatography coupled with tandem mass spectrometry (LC/MS2) method for the simultaneous quantification of rifampicin and its main active metabolite 25-desacetyl rifampicin in human plasma was developed and validated. The separation was performed on a Gemini NX C18 column under isocratic conditions using a mobile phase of 40:60 (V/V) methanol and 2mM ammonium formate in water, at 40 °C, with a flow rate of 0.6 mL/min. The detection of rifampicin and its metabolite was performed in multiple reaction monitoring mode using an ion trap mass spectrometer with positive electrospray ionization. The human plasma samples (0.1 mL) were deproteinized with methanol and aliquots of 0.3 μL from supernatants obtained after centrifugation were directly injected into the chromatographic system. The method shows a good linearity (r > 0.993), precision (CV < 8.2%) and accuracy (bias < 6.3%) over the range of 411 - 19737 ng/mL for rifampicin and good linearity (r > 0.992), precision (CV < 10.1%) and accuracy (bias < 8.2%) over the range of 70 - 3379 ng/mL for 25-desacetyl rifampicin. The lower limit of quantification (LLOQ) was 411 ng/mL and recovery was between 90.3-108.2% for rifampicin, whereas for 25- desacetyl rifampicin the LLOQ was 70 ng/mL and recovery between 93.1- 107.5%, respectively. The developed and validated method is simple, rapid and specific for the high throughput simultaneous determination of rifampicin and 25-desacetyl rifampicin in human plasma and was successfully applied in therapeutic drug monitoring of rifampicin in patients with tuberculosis. [ABSTRACT FROM AUTHOR]

Autoimmune thyroid diseases (AITDs), including Graves' Disease and Hashimoto's Thyroiditis (chronic autoimmune thyroiditis), are the most common organ-specific autoimmune disorders, occurring mostly in middle-aged women. AITDs are often associated with other autoimmune diseases such as vitiligo or systemic sclerosis (scleroderma), but there have been only few reports of AITDs concurring with CREST syndrome (Calcinosis, Raynaud's phenomenon, Esophageal dysmotility, Sclerodactyly and Telangiectasias), a limited form of scleroderma. Furthermore, these disorders have been associated with lymphoid malignancies, but only rarely with other cancers such as lung or breast. We report the case of a 59 year-old female patient who presented at the Endocrinology clinic for vertigo, dysphoria and fatigue. Clinical examination and serologic determinations revealed the diagnosis of an overlap syndrome between euthyroid autoimmune thyroiditis and CREST syndrome. Further investigations led to the detection of an incipient gastric adenocarcinoma which was promptly treated with total gastrectomy. [ABSTRACT FROM AUTHOR]

Aim: to investigate the effects of surgical stress on some biochemical parameters and the histopathological modifications in laboratory animals with induced hepathopathy. Material and methods: The experiments were carried out on 6 groups of Wistar rats, for two months: SF, E, MP, MPE, MK, MKE. In groups coded SF, normal saline solution was administered intraperitoneally. In groups coded E, experimental hepatopathy was induced by oral administration of ethanol. Midazolam (0.57mg/kgc/day, coded M), Propofol (15mg/kgc/day, coded P) and Ketamine (2mg/kgc/day, coded K) were administered in unique dose when rats were incised and sutured in the dorsal site. Postoperative, each group was divided in two parts (A and B). The subgroup A received Ketoprofen and the subgroup B received Acetaminofen. At the beginning and at the end of the experiment blood samples were taken from all animals and the following parameters were determined: cortisol, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) serum levels. At the end of the experiment the animals were sacrificed and the liver was harvested for histopathological evaluation. Results and discussion: Our study showed that chronic hepatopathy is associated with higher levels of cortisol, AST, ALT and LDH and the administration of MP or MK association accentuated these variations. The MP association and the postoperative Acetaminophen analgesia determined the most important modifications in the histopathological evaluation. Conclusion: The results proved that rats with alcohol-induced hepatopathy responded to surgical stress with higher levels of cortisol and hepathocytolysis enzyme levels. The histopathological evaluation showed that postoperative analgesia with Ketoprophen had a protective effect. [ABSTRACT FROM AUTHOR]

The aim of this paper was to investigate the local protective effect of an ointment containing 2% aqueous extract of Syringa vulgaris in animals exposed to ultraviolet radiation (UVR). Material and methods: The experiments were carried out on Wistar rats (180-200 g), divided in 4 groups of 10 animals each (coded L1-L4). The L1 group was the control group, the animals in L2 were exposed to UV, the rats in L3 received topical administration of the S. vulgaris ointment and the L4 group received the tested extract and was daily exposed to UVR. All the animals included in the experiment had their back hair removed. The groups exposed to UVR (λ = 100-400 nm) received 2.4 J/cm2, 15 minutes/day, 28 days. At the end of the experiment all the animals were sacrificed and we determined the superoxide dismutase (SOD) and malondialdehyde (MDA) activity levels and skin fragments from the exposed area were harvested for histopathological evaluation. Results and discussion: The animals exposed to UVR had higher values of SOD and MDA activity. The vegetable extract had a protective effect by reducing the variations of the enzymes activity in animals exposed to UV. The histopathological evaluation showed a smaller number of inflammatory cells in animals receiving the tested extract and UV exposure compared to the animals without any protection. The tested extract determined no histopathological variations compared to the control group. Conclusion: The tested extract showed protective effects without local toxicity and can represent a possible alternative to the products already on the market. [ABSTRACT FROM AUTHOR]

Nanoparticle drug carriers consists of solid biodegradable particles in size ranging from 10 to 1000 nm in which the active principle is dissolved, entrapped or encapsulated, and to which the active principle is absorbed or attached. Controlled release dosage forms cover a wide range of prolonged action formulations, which provide continuous release of their active ingredients at a predetermined rate and time. Among the drug carriers, vesicles are selfassembled colloidal particles used to encapsulate different substances within their interior, with broad usage in controlled drug release. The objective of this study consists in biocompatibility and in vivo evaluation of ketoprofen release from lipid vesicles coated in chitosan. The vesicles were prepared using an original method and thereafter, dialyzed for 10 hours, to remove their acidity. The ketoprofen vesicles were characterized for size and zetapotential by Malvern Zetasizer Nano ZS ZEN-3500. In vivo experiments were carried out on white Swiss mice (20-25 g), divided into 4 groups of 7 animals each treated orally (using an eso-gastric device) as follows: Group I (control): distilled water 0.1ml/10g body weight, Group II (Chit-lipid ves): Chitosan lipid vesicles 0.1ml/10g body weight; Group III (KET): ketoprofen 15 mg/kbw, Group IV (KET ves): ketoprofen vesicles 15 mg/kbw. The biocompatibility properties of ketoprofen vesicles were studied by assessing the effects on the blood, the serum biochemical and immune parameters. Ketoprofen release was evaluated using HPLC method, by determination of the substance blood levels in different time moments after oral administration in mice. Experimental protocol was implemented according to recommendations of the University Committee for Research. Data were statistically analyzed with SPSS software for Windows, version 17.0 and ANOVA method. We developed new carrier formulations that entrapped ketoprofen in lipid vesicles (mean size 491nm) with a moderate stability (mean Zeta potential +20.3mV). Laboratory analysis showed no significant differences of blood count, immune and biochemical parameters, between mice treated with entrapped or non entrapped ketoprofen thus indicates of good in vivo biocompatibility. The blood release kinetics study shows that ketoprofen loaded vesicles are capable of releasing the drug in a slow sustained manner. The biocompatibility studies suggest that ketoprofen lipid vesicles may be suitable for in vivo use as a drug delivery system. The use of soft matter vesicles as carriers for ketoprofen presented the advantage of drug sustained in vivo release comparing with non entrapped substance. [ABSTRACT FROM AUTHOR]

Nanoparticles for the purpose of drug delivery are defined as submicron colloidal particles. Nanoparticulate systems made of biocompatible and biodegradable materials such as polymers, either natural or synthetic, or solid lipids, can be used to deliver drugs to a specific position within the body. Vesicles are hollow spheres, commonly used to encapsulate labile hydrophilic molecules within their interior, and are important to be studied for developing new drug delivery vehicles to facilitate the absorption through the intestinal wall and transport substances into the blood. The objective of this study consists of in vivo evaluation of the effects of variation of ketoprofen soft matter vesicles dosage in cutaneous nociceptive reactivity. Ketoprofen vesicles prepared using an original method, were characterized for size and zetapotential by Malvern Zetasizer Nano ZS ZEN-3500. In vivo experiments were carried out on white Swiss mice (20-25 g), divided into 5 groups of 7 animals each treated orally (using an eso-gastric device): Group I (control): distilled water 0.1ml/10g body weight, Group II (KET 10): ketoprofen 10 mg/kbw; Group III (KET 15): ketoprofen 15 mg/kbw, Group IV (KET 10 ves): ketoprofen vesicles 10 mg/kbw Group V (KET 15 ves): ketoprofen vesicles 15 mg/kbw. Experimental protocol was implemented according to recommendations of the University Committee for Research and to the IASP Committee for Research and Ethical Issues guidelines. Data were statistically analyzed with SPSS software for Windows version 17.0 and ANOVA method. The ketoprofen vesicles were found to have a mean size of 491nm and mean Zeta potential of +20.3mV, value that suggest a moderate stability of the solution. The use of ketoprofen 15mg/kbw vesicles resulted in an increase of the latency time reaction to thermal noxious stimulation, statistically significant in the interval between 90 minutes and 10 hours after this new formulation administration. In the same experimental conditions ketoprofen 10mg/kbw vesicles determined an increase of the latency time response, statistically significant in the interval between 2 and 6 hours after substance administration. Both entrapped and non entrapped ketoprofen administration resulted in an analgesic effect in tail flick test. The use of soft matter vesicles as carriers for ketoprofen presented the advantage of drug sustained release, comparing with non entrapped substance in this somatic pain model. The effects of ketoprofen 15 mg/kbw vesicles were more intense and prolonged than those of ketoprofen 10 mg/kbw vesicles. [ABSTRACT FROM AUTHOR]

Copyright of Acta Medica Transilvanica is the property of Sciendo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Acta Medica Transilvanica is the property of Sciendo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Acta Medica Transilvanica is the property of Sciendo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Acta Medica Transilvanica is the property of Sciendo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

General anesthesia represents the induction of a balanced state of unconsciousness, accompanied by the absence of pain sensation and the paralysis of skeletal muscle over the entire body. Anesthesia is induced through the administration of anesthetic drugs and is used during major surgery and other invasive surgical procedures. General anesthetics may be given through a mask along with oxygen (gases or volatile liquids), or intravenously. Many drugs may interact with anesthetic medication causing different adverse effects. In this study we aimed to evaluate the drug-interactions in perioperatory period in laboratory animals with experimental-induced hepatopathy. The experiments were carried out on Wistar rats (190-200 g), divided in 12 groups of 6 animals each: SF, SFp, E, Ep, MP, MPp, MPE, MPEp, MK, MKp, MKE, MKEp. In groups coded SF, normal saline solution was administered intraperitoneally, 0.5 ml/100 g body rat/day, for 2 months. In groups coded E, experimental hepatopathy was induced by chronic oral administration of ethanol 13%, 0.5 ml/100 g body rat/day, for 2 month. 7 days before the end of the experiment, in groups coded „p" subcutaneous sterile cotton pellets were placed in the armpits. Midazolam (0.57 mg/kbw/day, groups coded M), Propofol (15 mg/kbw/day, groups coded P) and Ketamine (2 mg/kbw/day, groups coded K) were administered in unique dose, 3 days before the end of the experiment, when rats were incised and sutured in the dorsal site. At the beginning of the experiment (M0) and after 60 days (M1), blood samples were taken from all animals and the following parameters were determined: leukocyte formula, phagocytic capacity of peripheral neutrophils and serum complement activity. In the 60th day of the experiment, all animals were sacrificed, and from the groups coded „p", pellets were extracted together with their granulation tissue, desiccated and then weighted. Experimental protocols were implemented according to recommendations of the University Committee for Research and Ethical Issues. Our study showed that administration of Midazolam-Propofol association induced a higher local inflammatory process and systemic cellular immunossuppresion compared to Midazolam-Ketamine association. Despite the experimental conditions, the immunossuppresion was statistically significant higher in all animals with induced-granuloma and experimental alcoholic hepatopathy. Surgical stress (the practice of the incision) resulted in a local inflammatory process and a systemic immunosuppression, deeper in laboratory animals who received Midazolam-Propofol combination. The results proved that rats with alcohol-induced hepatopathy, treated with Midazolam-Propofol or Midazolam-Ketamine association presented an increased local inflammatory process, and a decrease of the systemic immune parameters. [ABSTRACT FROM AUTHOR]

Exposure to solar ultraviolet (UV) radiation is the main environmental factor in the initiation and development of skin cancer. In the same time, chronic wounds and acute trauma constitute well-established risk factors for development of epithelial-derived skin tumors, although the underlying mechanisms are largely unknown. The aim of this paper was to investigate the local and systemic modulator effects of aqueous extracts of Syringa vulgaris on some risk factors involved in skin carcinogenesis. The experiments were carried out on Wistar rats (180-200 g), divided in 10 groups of 6 animals each: SF, SFi, SFp, SFip, SV, SVi, SVp, SVpu, SVip, SVipu. Substances were administered intraperitoneally, in single daily dose, 28 days, as follows: groups coded SF received normal saline, 0.5 ml/100 g body rat/day; those coded SV received aqueous extract of S. vulgaris 136.25 mg/kbw/day. Groups coded „i” were exposed to UV radiation (λ = 100-400 nm), 2.4 J/cm2, 15 minutes/day, 28 days. In groups coded „p” were induced experimental lesions 7 days before the end of the experiment, and the lesions sizes were counted every day, during 7 days. In groups coded “u” 2% aqueous extract of S. vulgaris with oil-water emulsion and collagen ointment was applied topically in one daily dose. We also evaluated the following parameters: leukocyte formula, phagocytic capacity of peripheral neutrophils and serum complement activity. Experimental protocols were implemented according to recommendations of the University Committee for Research and Ethical Issues. Our study revealed that in groups treated with aqueous extract of S. vulgaris with or without topic application of oil-water emulsion and collagen ointment the healing process of lesions was speeded up comparing to the non-treated groups. UV exposure determined a significant decrease of the percent of neutrophils and lymphocytes, a reduction of phagocytic capacity of peripheral neutrophils and an increasing of serum complement activity, parameters that were not modified in the groups treated with aqueous extract of S. vulgaris ointment. UV irradiation determined an important immunosuppressant effect. Topical administration of aqueous extract of S. vulgaris in the form of oil-water emulsion ointment and collagen has fostered healing. Systemic administration of aqueous extract of S. vulgaris increased immunosuppression produced by irradiation, respectively irradiation and experimental lesion. We consider that this extract could promote lesion healing in immunocompromised organisms if administered topically but we recommend caution if using systemic administration. [ABSTRACT FROM AUTHOR]

The aim of this experiment was to study the api-diet influence on seric proteins profile (evaluated by electrophoresis) in rats with acetaminophen experimentally-induced hepatopathy. In order to reduce factors that precipitate the progression of hepatic lesions, we have administered api-therapy products. Substances: apitherapic products - Apiregya, ApiImunomod, ApiImunostim got from „Stupina SRL‟ (office and laboratories in the Balanesti parish, Gorj county, Romania, phone 0253.270.221). Animals were manipulated under general anesthesia with thiopental. The levels of investigated parameters were measured using an automatic analyzer (Aeroset, Abbott) and commercial kits (Abbott, USA). 60 white Wistar rats was used, equally divided into six groups: the control group - standard nourishment (group I); api-diet control group (group II); api-diet and royal jelly (RJ) control lot (group III); acetaminophen group (group IV); api-diet and acetaminophen group (group V); acetaminophen, api-diet , and RJ lot (group VI). After that, a number of 30 subjects were kept for study and research. Animals were kept in normal light and temperature conditions, water and food being provided ad libidum. Toxic hepatopathy was experimentally induced by acetaminophen administered by intra-gastric gavage (hydrous solution, 1g/kg/day, for 2 weeks). Animals were manipulated under general anesthesia with Thiopental. In group V, api-diet and acetaminophen co-administration determined a statistically significant increase of serum albimine level compared to: i) group I (standard nourishment control group) (30.42±1.27g/L versus 39.51±2.91g/L, p<0.0001); ii) api-diet control group (group II) (4.49±0.9g/L versus 39.51±2.91g/L, p<0.0001). In group VI, acetaminophen, api-diet, and RJ co-administration determined a statistically significant decrease of total globulins compared to: i) group I (standard nourishment control group) (69.57±1.27g/L versus 61.7±5.07g/L, p<0.0001); ii) group IV (acetaminophen) (95.51±0.9g/L versus 61.7±5.07g/L, p<0.0001). In group VI, acetaminophen, api-diet , and RJ co-administration determined a statistically significant decrease of γ-globulins compared to acetaminophen group (group IV) (9.83±1.2g/L versus 9.7±0.43g/L). Authors recommend apitherapy with Apiregya, ApiImunostim, and ApiImunomod in hepatic affections, but only taken into consideration the serum proteins electrophoresis profile. Also, treatment should be modulated according to the evolution of the above-mentioned parameters. [ABSTRACT FROM AUTHOR]

The aim of this experiment was to study the apidiet influence of hepatopathy induced by acrylamide, in rats. The objectives were to assess the following parameters: cholesterol and triglycerides, V-LDL, HDL, in terms of chronic hepatic injury induced by acrylamide, in rats. In order to reduce factors that precipitate the progression of hepatic lesions, we administered apitherapic products. Material and methods: Substances: apitherapic products - Apiregya, ApiImunomod, ApiImunostim get from „Stupina SRL‟ (office and laboratories in the Balanesti parish, Gorj county, Romania, phone 0253.270.221). Animals were manipulated under general anesthesia with Thiopental. The levels of investigated parameters were measured using an automatic analyzer (Aeroset, Abbott) and commercial kits (Abbott, USA). A number of 60 white rats Wistar race was used, divided equally in six lots: the control lot - standard nourishment (lot I), apidiet control lot (lot II), apidiet and royal jelly (RJ) control lot (lot III), acryl amide lot (lot IV), apidiet and acrylamide lot (lot V), acry amide, apidiet, and RJ lot (lot VI). After that, a number of 30 subjects were kept for study and research. Animals were kept in normal conditions for light, with access to water and food. Toxic hepatopathy was experimentally induced by acryl amide administered by intra-gastric gavage (hydrous solution, 50 mg/kg). Results and discussions: Apidiet + RJ administration (lot III) was efficient to keep the level of total cholesterol within normal limits. Apidiet + RJ administration in rats with previous acryl amide intoxication was efficient to hold the level of triglycerides within normal limits. No statistically significant differences between the studied lots were registered. This fact demonstrated the efficacy of apidiet+RJ administration in lot with previous acryl amide intra-gastric gavage, in order to maintain VLDL level. The increase of HDL cholesterol level certified benefic effect of apidiet + RJ nourishment after a previous intoxication with acryl amide. Conclusions: Authors recommend apitherapy with Apiregya, ApiImunostim, and ApiImunomod in hepatic affections due to toxic nutrition, in order to normalize the lipid profile. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO), formerly known as the endothelium-derived relaxing factor, is a mediator with a key role in the body, both in the central nervous system and in periphery. NO is synthesized by several cell types, where it acts as an autocrine and paracrine signaling molecule. Harnessing the impressive therapeutic potential of nitric oxide (NO) remains an ongoing challenge. In order to overcome the limitations linked with the use of nitric oxide and specially to increase the release of the radical in the targeted area, promising therapeutic strategies have been implemented, based on specific technologies which create releasing agents and vehicles for nitric oxide. Organic nitrites are the most known NO donor drugs, used especially in the treatment of cardiovascular diseases. In recent years, technological advances have allowed obtaining variations synthetic derivatives (such as diazeniumdiolates, S-nitrosothiols), which can generate NO in a controlled mode in the body and to chemically stabilize it; these compounds were studied with promising results in various animal models of vasospasm and pulmonary hypertension. Another high value therapeutic path is represented by the development of hybrid drugs (new nonsteroidal anti-inflammatory NO donor agents), with practical applications in inflammatory disorders accompanied by pain. Also, there is increasing evidence of the existence of NO donors with important antioxidant and hepatoprotective effects.

Hyperlipidemia is a well-known risk factor for coronary heart disease, the leading cause of death for both men and women. Current lipid-lowering treatment is not always efficient, therefore new pharmacological interventions that reduce LDL cholesterol (LDL-C) have been developed. This paper presents new class of specific LDL lipid-lowering drugs under investigation in phase II or III clinical trials. The inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9), a key enzyme in cholesterol homeostasis, improve the liver's ability to clear LDL from the plasma, reducing LDL-C levels. Currently, three monoclonal antibodies PCSK9 inhibitors (alirocumab, evolocumab and bococizumab) are evaluated in clinical outcome trials. ALN-PCSsc, the new first-in- class therapeutic RNA interference (RNAi) inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) is also the first-in-class investigational medicine that acts by turning off PCSK9 synthesis in the liver. The development leadership of ALN-PCSsc has now transferred from Alnylam Pharmaceuticals to The Medicines Company, who has initiated the ORION-1 Phase II study at the beginning of 2016. ALN-PCSsc has significant potential given its highly competitive profile as compared with monoclonal antibodies anti-PCSK9 MAbs, a recently approved class of LDL-C lowering drugs.

Aim: The study investigates the effects of magnesium nanovesicles on the memory processes performance in mice., Materials and Methods: L-a-phosphatidylcholine was used to obtain nano formulations as lipid vesicles systems stabilized thereafter with chitosan. The experiment was carried out on white Swiss mice, divided into 3 groups of 7 animals each, treated orally 7 consecutive days: Group I (Control): 0.1 mL/10g distilled water; Group II (Mg): 1 mmol/kbw magnesium chloride; Group III (Mg-vesicles): 1 mmol/kbw magnesium nanovesicles. The spatial memory performance was assessed by recording spontaneous alternation behavior in Y-maze test. Each animal was placed at the end of one arm and allowed to move freely through the maze during a single 8 min session. Alternation was defined as a consecutive entry in three different arms. The alternation percentage was computed according to the formula: (number of alternations/total number of arm visits--2) x 100. Data were analyzed using SPSS 17.0 software. Experimental protocols were implemented according to the recommendations of the University Committee for Research and Ethical Issues., Results: New carrier formulations entrapping magnesium chloride were designed: their mean size was 129.56 nm and the mean Zeta potential was +36.1 mV, indicating a moderate stability of the solution. Oral administration of magnesium vesicles resulted in a significant increase of spontaneous alternation percent in Y-maze test (p < 0.01), which suggests an improvement of short-term memory., Conclusions: Using magnesium chloride entrapped in lipid vesicles induced an enhancement of cognitive functions in mice especially by facilitation of learning extinction.

Aim: To investigate the effects of two serotonin receptor antagonists on spontaneous behavior in rats., Material and Method: The experiment was carried out on white male Wistar rats (150-200g) divided into 3 groups of 6 animals each, treated intraperitoneally with the same volume of solution as follows: Group I (Control): saline solution 0.1 ml/10 g weight; Group II (SB-269970): SB-269970 1 mg/kbw; Group III (NAN-190): NAN-190 1 mg/kbw. The effects of serotonin receptor antagonists on the spontaneous psychomotor skills of rats were tested in Actimeter LE-8811 (PanLab). The data were presented as mean +/- standard deviation and significance was tested by SPSS Statistics for Windows version 17.0 and ANOVA method. The experimental protocol was implemented according to the guidelines for handling and use of experimental animals of the Research Ethics Committee of the Iasi "Grigore T. Popa" University and ethical standards of the European Community., Results: The 5HT1 serotonin receptor antagonist NAN-190 determined a statistically significant reduction (p < 0.01) in both horizontal and vertical movements as compared with the control group, whereas the 5HT7 serotonin receptor antagonist SB269970 had no influence on rat behavioral manifestations., Conclusions: In our experimental conditions 1 mg/kbw NAN-190 decreased the total escape attempts, corresponding to a significant diminution of exploratory and self-maintenance spontaneous behavior in this experimental animal model. These manifestations may be correlated with the anxiolytic effect of 5HT1 serotonin receptor antagonist NAN-190 in rats. The administration of 5HT7 serotonin receptor antagonist SB-269970 did not alter the spontaneous activity in this behavioral experimental model in rats.

Aim: This paper is focused on the investigation the effects of two polymeric matrices for indomethacin in cutaneous pain models in mice. There were used two different co-polymers polyhydroxyethyl methacrylate and undecan, polymerization reactions being conducted under nitrogen, at 80 degrees C., Material and Methods: The experiments were carried out on white Swiss mice (20-25 g), divided into 6 groups of 7 animals each, treated orally. Biocompatibility properties of indomethacin-loaded copolymeric matrices ware evaluated by assessing the effects on the blood parameters, the serum biochemical tests of animals treated. The nociceptive somatic testing was performed using hot plate assay and tail immersion test. The latency (second) response to paw, respectively tail thermal noxious stimulation, was measured before the experiment and 15, 30, 60, 90, 120 minutes, 4, 6, 8, 10, 12 hours after the substances administration., Results: Laboratory analysis did not show significant differences of blood parameters, serum biochemical tests between control mice group (IND) and groups treated with 1 M, 1 IND, 3 M, 3 IND. In our experimental conditions IND determined a significant increasing of the latency period response, in hot plate and also in tail immersion tests. Using two different co-polymers for indomethacin incorporation we obtained an increasing of the latency time pain reaction in hot plate assay, respectively in tail immersion test, statistically significant (*p < 0.05) compared with the simple copolymers administration., Conclusions: We demonstrated that indomethacin co-polymeric matrices 1 IND and 3 IND determined similar immune responses with indomethacin and simple co-polymers after oral administration in mice, indicative of good in vivo biocompatibility. Oral administration of both 1 IND and 3 IND resulted in prolonged antinociceptive effects in hot plate assay and also in tail immersion test in mice.

Unlabelled: Self-medication with antimicrobial drugs is an important problem in the world and may lead to serious consequences for healthcare systems., Objective: To evaluate the prevalence and patterns of self-medication with antimicrobial drugs among university students in a Northeast region of Romania., Material and Methods: A cross-sectional questionnaire-based study was conducted to collect data from medical and non-medical students who lived in residence halls. Data were analyzed using descriptive statistics and the chi-square test, when applicable., Results: Out of the 320 questionnaires distributed, a total of 281 students completed and returned the questionnaires. Among these, 115 (41%) respondents admitted to have used at least one antibiotic in the six months prior to the survey, 44% of whom did not seek medical advice (irrational self-medication). The most common antimicrobial drugs used for self-medication were amoxicillin (37%), amoxicillin-clavulanate (33%), ciprofloxacin and penicillin (14%) and the most frequently reported reasons for self-medication were respiratory and oral infections (31%), common cold (25%), and genitourinary infections (20%). Some students mentioned the use of more than one antimicrobial drug, for more than one disease., Conclusions: self-medication with antimicrobial drugs is a relatively common practice among students in Romania. This suggests the need for interventions to prevent the irrational use of antimicrobial drugs, such as the implementation of national programs for public education regarding the risks and consequences for the health of irrational use of antimicrobials.

Aim: To evaluate drugs interactions with oral anticoagulants and their clinical relevance, in patients from two emergency departments in hospital., Material and Methods: Retrospective study, during one year, on patients (between 18 and 85 year old) with haemostatic disturbances admitted at two emergency departments in ,,Sf. Spiridon" Hospital, Iaşi and in Piatra Neamţ Public Hospital, consisted in medical records analysis: the diagnostic, therapy recommended. Data were scored and statistically analyzed by t test (Windows Excel). The experimental protocol was in agreement with recommendations of the "Gr. T. Popa" University Committee for Research and Ethical Issues., Results and Conclusions: Analysis and statistical processing of data shows that during the period of the study, 69 patients, which received oral anticoagulant therapy associated with different other medication belonged to the 60 and 80 years age group. The findings suggests the pathology is represented especially by atrial fibrillation and cerebral ischemic diseases. The correlation between the therapy consisting in OAC and amiodaronum or statines drugs association and International Normalized Ratio (INR), revealed a high level of anticoagulation and an increase of hemorragic complications.

Unlabelled: The depressing effects on the nervous central system (NCS) induced by benzodiazepines and ethanol are similar. The complications are rare in the benzodiazepine poisoning, but are a lot more frequent in association with other depressing drugs for the NCS (especially alcohol)., Material and Methods: We analyzed retrospectively patients with benzodiazepine poisoning admitted in the Internal Medicine Clinic - Toxicology during 2003 - 2009.The study attempted a complex evaluation of the consequences of acute and chronic alcoholism on the evolution of acute benzodiazepinepoisoning and the description of the clinic evolution and paraclinical particularities of the patients under investigation., Results: 343 patients with benzodiazepine poisoning were admitted, 150 were tested through measurement of alcohol level, leading to values between 1 - 415 mg/dl. Chronic alcoholism in personal pathological antecedents of the patients determined a relative risk of intoxication 1.46 times higher. The hospitalization period varied from 1 to 8 days for patients with chronic alcoholism and from 1 to 14 days for patients with acute alcoholism, a statistically important difference., Conclusions: During the period under investigation, from the total of patients admitted for acute benzodiazepine poisoning, 2 deaths were registered. Of the two deaths, one patient showed ethanol coingestion.

Aim: To investigate the effects of a Cetraria islandica extract in an animal model of hepatopathy., Material and Methods: The experiments were carried out on Wistar rats, treated intraperitoneally (excepting carbon tetrachloride which was administered orally by esogastric tube), at single daily dose, for 28 days and divided in eight groups of 6 rats each: Group 1: Saline solution (0.5ml/100g bw/day); Group 2: MgSO4 (5mg/kbw/day); Group 3: C. islandica (Ci) extract (21.56mg/kbw/day); Group 4: Ci+MgSO4; Group 5: carbon tetrachloride (CT).(0.1 ml/100g bw/day); Group 6: CT+MgSO4; Group 7: CT+Ci; Group 8: CT+Ci+MgSO4. At the end of the experiment blood samples were taken to assess the effects on the blood parameters,TGO, TGP, GGT, LDH, serum total billirubin, neutrophil phagocytic function (Nitroblue tetrazolium test) and serum complement activity. This parameters were determined with VITROS 750 XRC device, using Johnson&Johnson kits. The results were statistically processed with the help of "t-Student" test. p<0.05 was considered statistically significant., Results: In this carbon tetrachloride-induced hepatopathy animal model, C. islandica extract demonstrated hepatoprotective and immuno-stimulating effects (proved by normalization of glutamic-pyruvic transminase, glutamic-oxalocetic transminase, serum total billirubin, stimulation of neutrophils percentage and phagocytic functions, decreasing the carbon tetrachloride-induced basophilia and monocytosis, especially in association with magnesium)., Conclusions: Further studies are required to confirm the benefits of this association in hepatoprotective and immunomodulating therapies.

Aim: to investigate the influence of some stress factors on hepatic function and lipid metabolism in an experimental-induced hypertension., Material and Methods: The experiment was carried out on Wistar rats, treated intraperitoneally, for 4 weeks, as follows: Group 1: saline solution (0.5ml/100g weight); Group 2: saline solution + stress; Group 3: Endotelin-1; Group 4: Endotelin-1 + stress; Group 5: Endotelin-1 + cholesterol diet (0.2g/kbw/day); Group 6: Endotelin-1 + cholesterol diet + stress. Endotelin-1 0.25nmol/kbw was initially administered, followed by 0.5nmol/kbw 15 min later, 2 times/week. Stress-inducing factors were immobilization and water immersion. In the 28th day of the experiment blood pressure was measured and blood samples were taken from retro-orbitary plexus to assess glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) and lactic dehydrogenase (LDH) activity, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides levels., Results: Using immobilization and water immersion as chronic stress, our study proved an increase of GOT, GTP and total and LDL cholesterol in rats with endotelin-1-induced hypertension., Conclusions: In this animal model of endothelin-1-induced hypertension the blood pressure increased significantly under chronic exposure to stress, reaching the highest values when associating stress and experimentally induced dyslipidemia.

Aim: to study the effects of licht/dark induced-stress in an animal model of HELLP syndrome., Material and Methods: The experiment was carried out on white female Wistar rats treated intraperitoneally, for 4 weeks, as follows: Group 1: saline solution 0.5ml/100g weight; Group 2: saline solution + dark induced-stress, continuously, 28 days; Group 3: saline solution + light induced-stress, continuously, 28 days; Group 4: endotelin-l; Group 5: endotelin-1 + dark induced-stress, continuously, 28 days; Group 6: endotelin-1 + light induced-stress, continuously, 28 days. Endotelin-1 0.125nmol/kbw was initially administered, followed by 0.25nmol/kbw 30 min later, 2 times/week., Results: At the end of the experiment blood pressure was measured and blood samples were taken to assess: leukocyte formula, phagocytic capacity of peripheral neutrophils and serum complement activity, aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT) and lactic dehydrogenase (LDH) activity, total bilirubin and lipid profile., Conclusions: In these experimental conditions we obtained an animal model of partial HELLP syndrome (elevated liver enzyme levels and a low platelet count, values emphasized by light induced-stress, without hemolysis). In chronically stressed animals we found the highest levels of blood pressure, a decrease of plasmatic cortisol level and of phagocytic capacity of peripheral neutrophils and an increase of total cholesterol.

Unlabelled: Oral anticoagulants (OAC) are commonly used as a life-long therapy in the prevention of systemic embolism in patients with atrial fibrillation, valvular heart disease, prosthetic heart valves, and in the primary and secondary prevention of venous thromboembolism, in patients with acute myocardial infarction and angina pectoris. Drugs, herbs, and multivitamin supplements can alter the absorption, pharmacokinetics or pharmacodynamics of OAC., Aim: To investigate the possible interactions between oral anticoagulants and different drugs administered in patients in emergency department., Methods: This 1-year exploratory investigation on 93 patients on OAC (aged 30 - 85 years), admitted at two emergency departments of the Iasi "Sf. Spiridon" Hospital and Piatra Neamţ Hospital, consisted in their medical records analysis: diagnosis, recommended treatement. Data were scored and statistically analyzed by t-test (Windows Excel). The experimental protocol was in agreement with the recommendations of the Gr.T. Popa University Committee for Research and Ethical Issues., Results and Conclusions: Analysis and statistical processing of data shows that during the study period 56 patients which received oral anticoagulant therapy associated with different other medication belonged to the 60 and 80 years age group. This finding suggests that the pathology is represented especially by atrial fibrillation and myocardial infarction. The correlation between the therapy consisting in OAC and sartan or nonsteroidal anti-inflammatory drugs and International Normalized Ratio (INR), revealed a high level of anticoagulation and an increase in hemorragic complications.

Aim: Experimental researches on the effects of a Cetraria islandica extract, with or without magnesium association, on oxidative stress in rats., Material and Methods: The experiments were carried out on Wistar rats, treated intraperitoneally for 14 days at single daily dose as follows: Group 1: Saline solution (SS) (0.5 ml/100g bw/day); Group 2: Subcutaneous pellets, SS; Group 3: Levamisole (LEV) (10mg/kbw/day); Group 4: Subcutaneous pellets, LEV; Group 5: Prednison (PDN) (5mg/kbw/day); Group 6: Subcutaneous pellets, PDN; Group 7: MgSO4 (5mg/kbw/day); Group 8: Subcutaneous pellets, MgSO4; Group 9: C. islandica (Ci) extract (21.56mg/kbw/day); Group 10: Subcutaneous pellets, Ci; Group 11: Ci+MgSO4; Group 12: Subcutaneous pellets, Ci+MgSO4. At the end of the experiment blood samples were collected for assessing the following oxidative stress parameters: malonaldehyde, catalase, glutathione peroxidase, glutathione levels., Results: In the rats with or without experimentally-induced granuloma, repeated administration of Ci for 14 days resulted in a decrease of malonaldehyde, catalase, glutathione peroxidase activity, and an increase in glutathione levels. The association of magnesium augmented the antioxidant effect of Ci in this experimental model., Conclusions: In our study experimental conditions C. islandica extract determined adaptogenic-antistress effects, confirmed by its actions on oxidative stress parameters.

Aim: To determine the pharmacokinetics of glimepiride, a sulfonylurea antidiabetic agent, after single dose administration in healthy subjects., Material and Methods: Pharmacokinetic data for modeling were extracted from a single-center, randomized, single-dose, fasting state, two-way crossover bioequivalence study on 4 mg glimepiride in 24 healthy subjects., Results: Plasma concentrations of glimepiride were measured using a validated LC/MS/MS method. The pharmacokinetic parameters were calculated using non-compartmental analysis. Different pharmacokinetic models were tested to evaluate pharmacokinetics of glimepiride. The optimal model was chosen based on Akaike's Information Criteria., Conclusion: Compartmental analysis demonstrated that oral glimepiride tablets obey one compartment open model with rapid absorption following a first order kinetics and a short half-life.

Aim: to investigate the influence of some stress factors in endothelin-1-induced hypertension., Material and Methods: The experiment was carried out on Wistar rats, treated intraperitoneally, for 4 weeks, as follows: Group 1: saline solution (0.5 ml/100 g weight); Group 2: saline solution + stress; Group 3: Endotelin-1; Group 4: Endotelin-l + stress; Group 5: Endotelin-1 + cholesterol diet (0.2 g/kbw/day); Group 6: Endotelin-1 + cholesterol diet + stress. Endotelin-1 0.25 nmol/kbw was initially administered, followed by 0.5 nmol/kbw 15 min later, 2 times/week. Stress-inducing factors were immobilization and water immersion. In the 28th day of the experiment blood pressure was measured and blood samples were taken from the retro-orbitary plexus to assess plasma cortisol, blood count, phagocytic capacity of peripheral neutrophils, and serum complement activity., Results and Discussions: Repeated administration of endotelin-1 determined an increase in blood pressure, statistically significant in stress conditions comparing to non-stressed animals. Our study proved a decrease of plasma cortisol, total leukocyte count, phagocytic capacity of peripheral neutrophils, without significant alterations in serum complement activity., Conclusions: Chronic exposure to complex stress conditions in rats with endothelin-1-induced hypertension determined a decrease of plasma cortisol levels, effect correlated with elevated blood pressure and decrease in the number and phagocytic function of peripheral neutrophils.

Unlabelled: Pregnancy induced hypertension is a condition of high blood pressure during early and mid-pregnancy. This type of hypertension is much like the chronic type, but it occurs only when the woman is pregnant and resolves completely after delivery., Aim: to evaluate some stress hormones in both normotensive and hypertensive pregnant women., Material and Methods: The study investigated the correlation between pregnancy induced hypertension and different immune/inflammatory and other markers. This exploratory investigation was performed on pregnant women diagnosed with pregnancy-induced hypertension, admitted to the lasi Cuza Voda Hospital. The psychometric assessment was performed by using the daily stress test, daily hassle scale, blood pressure measurements, and determination of anthropometrical parameters. Some parameters, such as the neuroendocrine and immune/inflammatory ones, and specific parameters for pregnancy hypertension were determined., Results and Discussions: Our study revealed that blood pressure values presented significant differences between systolic, but not diastolic blood pressure values (p < 0.05). In 75% of subjects blood cortisol levels were not changed. Daily stress level assessment proved that low potential factors and an annoying environment had a high influence on both normotensive and hypertensive pregnant women. Hypertensive women also presented leukocytosis and thrombocytopenia., Conclusions: The research results showed that plasma cortisol level was higher in hypertensive pregnant women, compared with normotensives.

Unlabelled: Hypercholesterolemia plays an important role in atherosclerosis. The dietary supplementation of proteins or specific aminoacids seems to enhance the immune status in animals and humans with a complex pathological status, decreasing morbidity and mortality., Aim: In the present study we intended to analyse the effects of some nonpolar aminoacids--valine and leucine on cholesterol blood levels in a high-fat-diet in rats. In the same time we evaluated the vascular walls impact produced by the hypercholesterolemic diet., Material and Methods: Our experiment was realised on 32 male Wistar rats, which were fed with cholesterol, valine and leucine for 8 weeks. At the end of experiment we analysed serum levels of cholesterol and also histopathological features of hypercholesterolemia on the arterial wall., Conclusion: The results of our study indicate that valine and leucine decrease the serum cholesterol and therefore the hypercholesterolemic-induced prooxidant status of the body being useful in reducing atherosclerosis.

Aim: To evaluate immune system response, skin and hepatic reactivity in Swiss mice after retro auricular local administration of two textile dyes., Material and Methods: On 3 groups of white Swiss mice: group I (Cibacron Yellow F-4G), group II (Cibacron Orange P-2R) and control group (DMSO dimethylsulfoxide), substances were applied on left retro auricular ear, in dose of 25 microL solution 10% in DMSO (the dyes were not soluble in water), once a day, for 7 days. After euthanasia, blood samples were taken to assay differential cell count, peripheral neutrophils activity (NBT test), serum opsonic capacity, peritoneal macrophages activity (phagocytic and bactericidal capacity), and activity of spleenic T-lymphocytes with rossetting capacity, and spleen cells forming Jerne plaques. There were taken skin from local application of dyes, retro auricular and later cervical nodes from left side and hepatic samples., Results: Retro auricular and later cervical nodes mass increases after administration of textile dyes, compared to control group. Basophiles percentages were increased after administration of two dyes (stronger after yellow dye). Peripheral neutrophils activity was increased after administration of two dyes, especially after orange dye. Administration of the two dyes decreased serum opsonic capacity and peritoneal macrophages activity, but did not influenced the activity of spleenic T-lymphocytes with rossetting capacity and spleen cells forming Jerne plaques. There were significant skin and hepatic changes in microscopy., Conclusion: The studied dyes influenced the activity of immune system, increased skin and hepatic reactivity.

Unlabelled: Reactive Red 183, Reactive Red 2 and Reactive Blue 204 (red dye, green dye and blue dye) are three reactive dyes frequently used in textile industry. In some atmospheric conditions ( high temperature, perspiration, pH values, UV/IR radiations), some quantities of these hydrolyzed dyes, could pass from textile clothes directly into the human skin., Material and Method: There were used 4 groups of white Swiss mice (with similar weight and number of both sexes), control group and 3 groups, treated once daily with a retro-auricular application of different reactive dyes. After 14 days of treatment, blood samples were taken from retro-orbitary plexus to assess leukocyte count, phagocytic capacity of peripheral neutrophils, serum opsonic capacity, phagocyte capacity and bactericidal capacity of peritoneal macrophages, splenic T lymphocytes with rossetting capacity and spleen cells forming Jerne plaques. The retro-acuricular and latero-cervical nodes were weighted., Results: Red dye did not influence the weight of the studied nodes, but determined statistically significant modifications on non-specific immune system parameters. Blue and grena dyes determined modifications of weight especially of retroauricular nodes. Grena dye determined important effects of non-specific immune system parameters (serum opsonic capacity, phagocyte capacity and bactericidal capacity of peritoneal macrophages). The blue dye did not determine a biological response., Conclusion: Red and green dye determined important effects on non-specific immune system parameters.

Unlabelled: The effects of the saponinic summ extracted from roots of Aralia mandshurica have been studied in experimentally animals exposed to stress., Material and Methods: The experiment was carried out on 4 groups of animals divided into 24 lots of 12 white rats each with experimentally induced chronic inflammation or/and exposed to stress induced by exposure to continuous dark or light. The drugs (Levamisole (LVM) (10mg/kg bw/day), Indometacin (IND) (1.42 mg/kg bw/day), Extract of the roots of Aralia mandshurica (SAR) (26.25 mg/kg bw/day) and saline solution (0.5 mL/100 g bw/day) were administered orally for 14 days, in unique daily dose. Blood samples were taken from rats' retroorbital plexus before the beginning of the treatment protocol (M0) and at the finish of the treatment (M1) in order to assay differential cell count, peripheral neutrophils activity (NBT test) and serum complement activity., Results: The SAR extracts exert influence on immunity defence cellular's components without influence on humoral efects, no matter of experimentally conditions. They determined decreasing of the percentage of the neutrophils in peripheral blood (at the lower levels than Indometacin (IND)., Conclusion: The experimental results demonstrated immunomodulatory effect of this saponine extract.

Three topical formulae with Allium cepa L. extract 30% (w/w) were studied for the evaluation of their release profiles of flavonoids and for their potency on experimental wounds on mice. The rates of release were performed under occluded conditions using cellulose acetate membrane. Data obtained from the in vitro release show that the gel formula F1 is the most efficient in the membrane diffusion process. The rate of wound healing was assessed by the contracting ability and the period of epithelization. The most important effect in the contracting ability was noticed in the case of F2 formula.

In order to continue the research of the rutin semisynthetic derivatives we obtained some new morpholine and piperidine derivatives. Melting points, solubility, yield, C, H, N elemental analysis and UV spectra characterised all of these compounds. The toxicity was established by intraperitoneal administration at mice; the values of LD50 are between 743.75 and 856.25 mg/kg (medium toxicity). Pharmacological assays included the following parameters: leukocytes formula, NBT test, and serum complement activity. The new derivatives of rutin have a very good solubility in water, a pH closed to physiological value and immunosuppressive activity: peripheric blood PMN and lymphocytes are decreased; fagocytic capacity of peripheric blood PMN is also decreased; serum complement activity is not changed.