Method of treating drug sialoadenopathy
SUBSTANCE: vitamins A and E, novocaine blocades of parotid salivary glands, intake of potassium iodide solution, intake of galantamine, additionally administered is "Vezugen" in a dose of 2 tablets (capsules) 2 times per day for 30 days are administered.
EFFECT: invention makes it possible to stimulate the formation of own saliva in patients in case of drug sialoadenopathy, conditioned by chemotherapy of malignant tumours.
The invention relates to medicine, namely to surgical dentistry and maxillofacial surgery, and can be used in the treatment of drug sialadenitis caused by chemotherapy of malignant tumors of any localization.
Known physiotherapeutic method of treatment of diseases of the salivary glands, namely, ultrasonic therapy is the area of the temporomandibular joint. The method is carried out in a pulsed mode (pulse duration 1-10ms), the technique of the movable contact of the vibrator straight. The intensity of 0.05-0.2 W/cm2, duration 3-5 minutes, every other day ("Physiotherapy Handbook" ed. by I. N. Sosina, Kiev, 1973).
A method of treating diseases of the salivary glands by acoustic stimulation, characterized in that conduct a prolonged influence on the neuro-muscular tissues of the maxillofacial region with an audible oscillation frequency 2.4 to 3.3 kHz, the sound pressure of not less than 1 PA at a length of 0.15 to 12 hours (Patent RF №2110247).
A method of treating diseases of the parotid salivary glands at points VB2 (ting-Hui), E6 (Chia-che), E7 (Xia-Guan), and for diseases of the submandibular salivary glands at the point E5 (Yes-in) produce production 1 leech at a point in time prior to the full cavansite the course of treatment 9 to 11 treatments for men and 8 to 10 for W�NSIN with an interval of two-three days alternately on the right and left salivary glands (Patent RF №249947).
The known method of treatment that is carried in the salivary glands of rats applied drug that contains diclofenac-sodium - 1 wt.% and glycerogel silicon as helium basics - the rest. The application of the drug is administered daily single dose of 50 mg/kg on an area of not more than 4 cm2. The course of treatment - no more than 14 days. The invention allows to quickly arrest the inflammation by using only local drug action due to its high transcutaneous conductivity and anti-inflammatory activity (Method of treatment of inflammatory diseases of the salivary glands - RF patent №2323723).
For the treatment of drug sialoadenitis arising after chemotherapy of malignant tumors of different localization, is restorative therapy and treatment, aimed at increasing the secretory function of the salivary glands (I. F. Romacheva, L. A. Yudin, V. V. Afanas'ev, A. N. Morozov. Diseases and injuries of the salivary glands. - M.: Medicine, 1987. - P. 69), as well as substitution therapy with use of artificial saliva or irrigation of the oral cavity infusions of herbs: chamomile, sage (Matina V. N. Diseases and tumors of the salivary glands. In: "Diseases, injuries and tumors of the maxillofacial localization, a Handbook of clinical dentistry edited by Professor A. K. Iordanishvili. - SPb.: With�Eclat, 2007. - S. 230). These funds are used in medical practice to ensure irritating to the epithelium of the salivary glands with the purpose of increasing its excretory activity to develop their own saliva or for the purpose of replacement of liquids saliva that does not increase the quality of life of patients.
All these methods have their positive and negative sides. The first method does not always improve the production of natural saliva and optimizes the production of saliva, causing dryness of the mouth, which is painful for the patient. The second method is ineffective.
The closest in technical essence is a method aimed at improving the function of the salivary glands to develop natural saliva due to the irritating action on the secretory epithelium of the salivary glands and providing, on the background of strengthening therapy with vitamins A and E, treatment aimed at enhancing the secretory function of the salivary glands, which use novocaine blockade of the parotid salivary glands 2 times a week during the month, a 2% solution of potassium iodide orally 1 table spoon 3 times a day, galantamine inside a 0.5% solution of 1 ml on an empty stomach daily for 30 days (I. F. Romacheva, L. A. Yudin, V. V. Afanas'ev, A. N. Morozov. Diseases and injuries of the salivary glands. - M.: Medicine, 1987. - P. 69). Complex data prep�the ATA allows you to stimulate your own saliva reducing the patients of the phenomenon of dryness in the mouth.
The disadvantages of this method are a slight increase in the secretory function of the salivary glands.
The purpose of the invention - improving the efficiency of treatment of drug sialoadenitis of the salivary glands caused by chemotherapy of malignant tumors of any localization, aimed at improving their excretory functions.
This object is achieved in that in the treatment of patients of drug sialoadenitis of the salivary glands caused by chemotherapy of malignant tumors, apply restorative therapy with vitamins a and E, and use novocaine blockade of the parotid salivary glands, shall receive a 2% solution of potassium iodide, galantamine and additionally with the start of treatment of the disease is prescribed "Vasogen" 2 capsules (tablets) 2 times a day with meals for 30 days.
"Vasogen" - dietary Supplement, developed on the basis of peptide complex that contains amino acids. Previously this tool was not used as irritating the secretory epithelium of the salivary glands and used for another purpose, namely to normalize the functional state of blood vessels in the complex treatment of patients suffering from atherosclerosis vessels of the heart, brain and lower limbs, impaired microcirculation different org�new and tissues in the psycho-emotional stress, as well as for the prevention of vascular diseases in elderly and senile age.
Biological active food Supplement "Vasogen" created LLC "Chemical-biological Association at Russian Academy of Sciences "Firm Vita" in the form of capsules or tablets based on amino acids (certificate of state registration № RU 77.99.11.003, E.0511 dated 04.05.2011).
In our technical solution is proposed to use the tablets (capsules) "Vespene" as a General means of sensitizing the secretory epithelium of the salivary glands and stimulating the formation of his own saliva in drug sialadenitis caused by chemotherapy of malignant tumors of any localization.
The method has been tested in a clinical setting in the treatment of drug sialadenitis caused by chemotherapy of malignant tumors.
Positive therapeutic effect was observed in all cases. He was to increase education amount of saliva in patients with drug sialadenitis caused by chemotherapy of malignant tumors.
Here are clinical observations.
Example 1. E. the patient, 60 years old, came with complaints of dryness in the mouth, the Ambassador of chemo therapy of malignant tumors of the middle part of the neck on the right. Last� completion of chemotherapy it took 19 days. The amount allocated to its own saliva in 20 minutes was 1.6 ml.
Diagnosed drug sialadenitis caused by chemotherapy of malignant tumors of the neck.
Appointed: vitamins A and E, procaine blockade of the parotid salivary glands 2 times a week during the month, a 2% solution of potassium iodide orally 1 table spoon 3 times a day, galantamine inside in the form of a 0.5% solution of 1 ml on an empty stomach daily for 30 days.
After 30 days notes some improvement, the amount allocated to its own saliva in 20 minutes 2,34 ml.
Example 2. Patient G., 65 years old, came with complaints of dryness in the mouth after chemotherapy of malignant tumor of the right breast. After chemotherapy it has been 25 days. The amount allocated to its own saliva in 20 minutes was 1.3 ml.
Diagnosed drug sialadenitis caused by chemotherapy of malignant tumor of the right breast.
Appointed: vitamins A and E, procaine blockade of the parotid salivary glands 2 times a week during the month, a 2% solution of potassium iodide orally 1 table spoon 3 times a day, galantamine inside in the form of a 0.5% solution of 1 ml on an empty stomach daily for 30 days and 2 capsules (tablets) 2 times a day with meals for 30 days biologically active food supplements "Vasogen".
After 30 days notes W�acetelyne improvement, the amount allocated to its own saliva within 20 minutes of 4.3 ml.
A method for the treatment of drug sialadenitis caused by chemotherapy of malignant tumors of different localization, with vitamins A and E, novocaine blockades of the parotid gland, 2% solution of potassium iodide inside, galantamine inside in the form of a 0.5% solution of 1 ml on an empty stomach daily for 30 days and the admission of the drug "Wespen", allows during the month to provide a significant improvement in the education of their own saliva in patients undergoing radiation therapy in the face.
A method for the treatment of drug sialadenitis caused by chemotherapy of malignant tumors of any localization, by taking in vitamins A and E, the use of novocaine blockades of the parotid salivary glands, solution of potassium iodide inside solution inside of galantamine, characterized in that additionally use the drug "Vasogen" 2 tablets (capsules) 2 times a day for 30 days.
SUBSTANCE: 20-25 minutes after surgical intervention, a mouth bath of an implantation area with the Tonsinal phytopreparation diluted in an amount of 2.5 g in 100 ml of boiled water of room temperature is executed. 20-25 minutes later the Plastin CM-1 phytopreparation is applied on the alveolar process mucosa within the implantation area from the vestibular side for 1.5-2 hours. That is preceded by the desalivation of the oral cavity and mouth rinsing carefully with the Tonsinal solution trying to avoid any dynamic movements. The above procedures are performed 3-4 times a day for at least 10 days.
EFFECT: more effective dental implantation by improving microcirculation, fast normalising of oral microbiocoenosis, wound surface healing by immediate union, reliable implant attachment to gums and providing the implant stability.
SUBSTANCE: group of inventions relates to medicine, namely to dentistry, and can be used for the treatment of conditions, related with the increased expression of MMP-13, selected from the group, consisting of loss of one or more teeth fixation, teeth loss, teeth mobility, formation of recesses, bone tissue loss and a combination of two and more of the said conditions. For this purpose the application of 4-acetamidophenyl 2-isopropyl-5-methylcyclohexylcarbonate in the production of a medication for the treatment of the said conditions is claimed. A composition for teeth care, containing an orally acceptable carrier and a therapeutically effective quantity of a MMP-13 inhibitor in the form of 4-acetamidophenyl 2-isopropyl-5-methylcyclohexylcarbonate is also claimed.
EFFECT: group of inventions provides the effective treatment of the said conditions die to effective MMP-13 suppression.
3 cl, 5 tbl, 5 ex
SUBSTANCE: method involves professional oral hygiene is carried out consisting in ultrasonic removal of supra- and subgingival dental deposits and polishing of supragingival teeth. Bite splinting and recovery of dentition integrity may be required. After dissecting a mucoperiosteal flap according to the known technique, an incision area is sanitated by means of a photodynamic therapy (PDT). The PDT is conducted with the use of a diode laser at wave length 660±5 nm and emitting power 0.5-1.0 Wt. The photosensitiser "Photoditasin" in the form of 0.5% gel is introduced by means of a cannula into dental gaps, under the dissected segments of the flap and onto the mucosal tissue for 5 minutes. The photosensitiser is washed out, and the gingival pockets are repeatedly exposed to laser light for 2-3 min in the same environment. Sterile osteoplastic material is introduced into bone defects, and the flap is sutured together.
EFFECT: effective cleansing of the surgical area, eliminating the periodontal inflammation, stimulating tissue osteogenesis and regeneration, stabilising the processes of bone tissue absorption of alveolar interdental septa and preserving the tissues.
2 cl, 1 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to the pharmaceutical industry, namely to an oral care composition and to a method for increasing the solubility of an active ingredient recovered from magnolia extract - tetrahydrohonokiol. The oral care composition contains an active ingredient recovered from the magnolia extract - tetrahydrohonokiol, propylene glycol and an orally acceptable carrier, in a certain amount.
EFFECT: content of the certain amount of propylene glycol in the oral care composition increases the solubility of tetrahydrohonokiol that leads to improving the effectiveness of its delivery and bioavailability.
3 cl, 8 tbl, 8 ex
SUBSTANCE: invention relates to medicine and is intended for oral cavity care. Compositions include a multi-layered film and an orally acceptable carrier. The carrier contains the first flavouring agent, with the second flavour being contained in the present central layer of the multi-layered film, located between two external surface layers. The first and second flavouring agents can be similar or different. Each film layer can include a film-forming polymer, for instance, hydroxypropylmethylcellulose. The external layers can include a substance, modulating the release of the flavouring agent, for instance, polyvinylacetate or hydroxymethylcellulose. The carrier can be a means for teeth cleaning or a liquid for mouth rinsing.
EFFECT: obtaining the composition for oral cavity care.
22 cl, 3 dwg, 4 tbl, 11 ex
SUBSTANCE: vaseline-lanolin (2:1) based ointment 74.0 g is added with a 40% herbal alcoholate 25 ml of the following composition (in the mixture of a herbal raw material: alcohol base - 1:5), weight fractions: nodding catchfly herb - 3 weight fractions, pot marigold blossom - 1 weight fraction, spiraea herb - 1 weight fraction, with the ointment added with clove oil 1.0 ml. The prepared ointment is applied on inflamed periodontal and oral mucosal tissues for 20 minutes 2-3 times a day for 14 days; the patient is advised not to drink or eat for 1 hour.
EFFECT: method enables increasing clinical effectiveness by combining high antimicrobial, immunomodulatory, anti-allergic and keratoplastic activity and ease of use.
SUBSTANCE: on completion of the antibacterial course, sodium hyaluronate in the form of a gel is single administered by means of a syringe with a needle of 2 cm long or more under an oral mucosa along a transitory fold into the points within projections of apexes of dental roots 1.4, 2.4, 3.6, 4.6 and into a point on the mid-line of projections of apexes of anterior roots of upper and lower jaw respectively. The needle is brought under the mucosa on the lower jaw by transecting the projections of an alveolar counterfort line. On the upper jaw - by transecting the projections of the upper counterfort line. While removing the needle from the mucosa, the syringe content is squeezed out. Sodium hyaluronate is administered into both jaws in an amount of 3.0 to 4.4 ml.
EFFECT: method enables increasing the jaw bone density within counterforts, as well as soft and bone tissues of periodontium.
4 tbl, 16 dwg, 3 ex
SUBSTANCE: invention refers to dentistry and concerns treating chronic generalised periodontitis. Implementing the above method is ensured by a complex preparation in the form of an ointment of the following composition: Vaselin - lanolin base (1:1) - 88.5 g, 70% ipecac infusion - 5.0 g, 70% scholar tree - 5.0 g, Ecdysterone - 0.02 g; eucalyptus oil - 1.0 g. The oil is applied as a therapeutic periodontal applicate on a gingival surface following application anaesthesia with 10% lidocaine, chairside oral hygiene, drug-induced treatment of the gingival margin with 1% Iodinolum and separation of salivary glands in the oral cavity, once a day for 2 hours for 4 weeks; the patients are recommended not to eat or drink for two hours. The preparation composition particularly provides capillary-reinforcing, anti-inflammatory, reparative and anaesthetic action.
EFFECT: method of treating is easy to use, physiologically-friendly, and provides the complete recovery.
SUBSTANCE: invention relates to a compound of formula (I) : or a salt thereof, wherein R1 and R5 are independently selected from H, OH and alkoxy; R2-R4 and R6-R8 are independently selected from H, OH, F, Cl, Br and I; R9 and R10 are C2-C8 alkenyl; under the condition that at least one of R1, R5 and R7 is OH or alkoxy; at least one of R2-R4, R6 and R8 is F, Cl, Br or I; and R2 and R6 are Cl. The invention also relates to an antibacterial composition and treatment methods.
EFFECT: improved properties.
18 cl, 7 ex, 10 tbl
SUBSTANCE: agent for treating inflammatory periodontal and oral mucosal diseases associated with Helicobacter infection contains silicone glycerohydrogel of Si(C3H7O3)4·6C3H8O3·24H2O and bismuthate tripotassium dicitrate of formula [HOC(CH2COO)2COO]2K3Bi in the following proportions, wt %: bismuthate tripotassium dicitrate 1.0-2.5; silicone glycerohydrogel - the rest up to 100. The method of treating inflammatory periodontal and oral mucosal diseases consists in a combination of systemic standard anti-Helicobacter therapy and a local effect of the above agent on the involved region. Particularly, treating periodontitis is ensured by applying the agent on the gingival surface and introducing it into the gingival pockets once a day for 10 min; the therapeutic course makes 5-6 days. The oral mucosal diseases are treated by applying the agent 0.1 mm thick with a glass spatula on the involved oral mucosa 2 times a day; the therapeutic course is 12 days.
EFFECT: formulation of the agent provides achieving the high therapeutic effect; the dosage form is easy to be applied locally.
4 cl, 2 dwg, 1 tbl, 2 ex
SUBSTANCE: skin regeneration is stimulated by using a synthetic analogue of indolicidine, a natural antimicrobial peptide having formula H-Lys-Lys-Pro-Trp-Lys-Trp-Pro-Lys-Lys-Pro-Trp-Arg-Arg-NH2.
EFFECT: accelerating reparative skin regeneration following a burn injury.
2 tbl, 1 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to biotechnology, more specifically to MUC1 cytoplasmic domain peptides, and can be used in the anticancer therapy. A method for inhibiting MUC1-positive cancer cell in an individual involves administering into an individual the MUC1-peptide of the length of at least 6 sequential MUC1 residues and no more than 20 sequential MUC1residues and containing the sequence CQCRRK, wherein the amino terminal cysteine from CQCRRK is closed at its NH2 terminal by at least one amino acid residue, which shall not conform with the native transmembrane sequence MUC-1. Alternatively, there can be used MUC-1 peptide of the length of at least sequential MUC1 residues and no more than 20 sequential MUC1 residues, which contains the sequence CQCRRK with all amino acid residues of the above peptide being D-amino acids.
EFFECT: invention enables inhibiting MUC1oligomerisation effectively and inducing the tumour cell apoptosis and the tumour tissue necrosis in vivo.
80 cl, 16 dwg, 1 tbl, 3 ex
SUBSTANCE: invention represents method of preparing viscoelastic protector of corneal endothelium, including dissolution of initial therapeutic component with excessive viscosity in phosphate buffer, filtration and sterilisation until required viscosity value is obtained, characterized by the fact that as initial therapeutic component used is 3% solution of native hyaluronic acid, after dissolution 1% peptide complex, consisting of amino acid desmosine and following short-chained peptides-oligopeptides: GlyTrpIle; IleAspIle; PheArgPro; GlnHisHis; ProHisTyr; ThrTrpTrp; LysPheThr; LysArgMet; PheCysMet; IleIle; AspLysLys; TrpPro; GluThr, is introduced, and sterilisation is carried out by ionizing radiation in the range of radioactive radiation from 78×107 Mrad to 11×108 Mrad.
EFFECT: recovery of biochemical processes in endothelial layer of cornea with constant eye cornea moistening and increase of biocompatibility, which contributes to fast rehabilitation after traumas or surgery.
FIELD: medicine, pharmaceutics.
SUBSTANCE: presented solutions relate to field of immunology. Claimed are: pharmaceutical, containing peptide, obtained from HIG2 or URLC10, capable of inducing cytotoxic T-lymphocytes (CTL) by formation of antigen-presenting complex with antigen HLA-A0206. Described are isolated antigen-presenting cell and CTL and methods for their induction. Antigen-presenting cell is induced by contact of cell, expressing antigen HLA-A0206, with peptide, obtained from HIG2 or URLC10. Cytotoxic lymphocyte is induced by contact of CD8-positive T-cell with antigen-presenting cell, presenting on its surface complex of antigen HLA-A0206 and peptide, obtained from HIG2 or URLC10. Characterised are method and means of immune anti-tumour response induction by introduction to patient of medication, which contains peptide, capable of inducing CTL.
EFFECT: claimed inventions can be used in treatment of cancer disease, characterised by higher expression of HIG2 or URLC10.
12 cl, 8 dwg
SUBSTANCE: 30-60 minutes after the following fraction of radical irradiation on the 1st, 3rd and 5th day of each week for the whole period of irradiation, the preparation Molixan® 60 mg (2 ml) is introduced intramuscularly to the patient.
EFFECT: higher efficacy and safety of the chemotherapy ensured by relieving the manifestations of oral mucositis.
4 tbl, 2 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: group of inventions refers to compositions and methods for prevention or treatment of renal fibrosis in an individual. Particularly, the method for prevention or treatment of renal fibrosis in an individual involves administering a composition containing a pharmaceutically effective amount of a vasoactive intestinal peptide (VIP) or one or more functional VIP fragments specified in VIP(10-28), VIP(4-12), VIP(4-16), VIP(4-20), VIP(4-24), VIP(6-10), VIP(6-12), VIP(6-16), VIP(6-20), VIP(6-24) or conventional substitutes thereof into the individual exposed to a risk of developing renal fibrosis or suffering from renal fibrosis.
EFFECT: using the group of invention enables preventing or delaying developing renal fibrosis in the individual more effectively.
15 cl, 4 dwg, 2 ex
SUBSTANCE: conduit wall is presented by a material of random micro- and nanofibres of a bioresorptive polymer of poly(ε-caprolactone), and the content is presented by a self-assembled nanostructured hydrogel of acetyl-(Arg-Ala-Asp-Ala)4-CONH2(PuraMatrix™) oligopeptide. The above conduit is implanted in a complex with the direct local delivery of vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2) genes to be introduced into the proximal and distal nerve segments, while the formed conduit is implanted into a nerve rupture, and its ends are fixed with epineural sutures.
EFFECT: invention provides a stimulating effect on the invasion of regenerative medullated fibres, on the recovery of motor and sensitive nerve function, and enables improving the effect of the recovery of the nerve structure and function after the extended ruptures.
SUBSTANCE: invention relates to biochemistry and biotechnology and can be used in the pharmaceutical industry to produce drugs for treating conditions, which involves inhibiting dipeptidyl peptidase IV (DPPIV). Proposed is use of the disclosed inhibitors as a means of suppressing the function of DIPPIV through direct administration thereof and as part of a pharmaceutical composition.
EFFECT: obtaining a group of novel peptides, having DIPPIV inhibitor properties, which enable to reduce enzyme activity by at least 25%.
9 cl, 1 tbl, 11 dwg, 5 ex
SUBSTANCE: invention relates to a peptide capable of binding with scurfin and inhibiting biological activity of scurfin, which is selected from a peptide consisting of an amino acid sequence Arg-Asp-Phe-Gln-Ser-Phe-Arg-Lys-Met- Trp-Pro-Phe-Phe-X, where X is absent or X is present and represents X14 or X14-X15, where X14 and X15 independently denote an amino acid, a version of said peptide and a pharmaceutically acceptable salt thereof. The invention also discloses a fused protein and a pharmaceutical composition, which involves use of said peptide and fused protein, as well as use thereof to produce and treat pathologies which require transient regulation or inhibition of immunosuppressive activity of regulatory T lymphocytes, such as a neoplastic disease or infectious disease. The invention also relates to a method of producing said peptide and fused protein, including a protein or peptide coding nucleic acid, a DNA construct, an expression vector and a host cell.
EFFECT: invention provides effective treatment of infectious and neoplastic diseases which require transient regulation or inhibition of immunosuppressive activity of regulatory T lymphocytes.
26 cl, 10 dwg, 5 ex
SUBSTANCE: composition for improvement of brain function as active ingredient includes peptide X-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Y (where X is absent or represents He or Asn-Ile; and Y is absent or represents Val-Met), peptide X-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu-Y (where X is absent or represents Thr-Gln-Thr-Pro, Pro-Leu-Thr-Gln-Thr-Pro, Leu-Thr-Gln-Thr-Pro or Pro; and Y is absent or represents Val-Met) or their salts. Method for improvement of brain function involves introduction of the above peptide or its salt.
EFFECT: invention allows effective prevention of amnesia and strengthening of memory at peroral use of a low dose of the above peptides.
35 cl, 6 dwg, 6 ex
SUBSTANCE: CEA, CA 19-9, CA 72-4, M2-PK cancer-specific markers and Ki-67 proliferation index are pre-determined; combined positron emission and computer tomography (PET/CT) are performed. Up to two procedures of neoadjuvant intra-arterial chemoembolisation are conducted with the first one performed by administering a half single systemic dose of irinotecan in lipiodol 4-6 ml; no sooner than 2-3 weeks later, the cancer-specific markers and Ki-67 proliferation index and PET/CT SUVmax are checked; if at least one of this factors tends to increase as compared to references, the intra-arterial chemoembolisation is conducted again by administering at least 1/3 single systemic dose of irinotecan in no more than lipiodol 5 ml. Not later than 10-14 days following the second chemoembolisation or no sooner than 2-3 weeks after the first chemoembolisation, a surgical intervention is required if the tumour keeps its metabolic and proliferative activity on these days.
EFFECT: method enables decreasing the tumour process activity and performing the surgical intervention at the moment of extreme devitalisation of the tumour and micro-disseminates, and thereby improving the remote therapeutic effects.
2 cl, 4 dwg, 3 ex