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English to Latvian: Pharmacy General field: Science Detailed field: Medical: Pharmaceuticals
Source text - English CLAIMS
1. A parenteral pharmaceutical formulation comprising a pharmaceutically acceptable base addition salt of a boronic acid of formula (I):
wherein
Y comprises a hydrophobic moiety which, together with the aminoboronic acid residue
–NHCH(R9)-B(OH)2, has affinity for the substrate binding site of thrombin; and
R9 is a straight chain alkyl group interrupted by one or more ether linkages and in which the total number of oxygen and carbon atoms is 3, 4, 5 or 6 or R9 is –(CH2)m-W where m is 2, 3, 4 or 5 and W is –OH or halogen (F, Cl, Br or I),
and, when YCO- is an optionally N-terminally protected dipeptide residue, the peptide linkages in the acid are optionally and independently N-substituted by a C1-C13 hydrocarbyl group optionally containing in-chain or in-ring nitrogen, oxygen or sulfur and optionally substituted by a substituent selected from halo, hydroxy and trifluoromethyl.
2. A formulation of claim 1 wherein R9 is an alkoxyalkyl group.
3. A formulation of claim 1 or claim 2 wherein all the peptide linkages in the acid are unsubstituted.
4. A formulation of claim 1 or claim 2 wherein said C1-C13 hydrocarbyl group is a C1-C6 saturated hydrocarbyl group.
5. A formulation of any of claims 1 to 4 wherein YCO- comprises an amino acid which binds to the S2 subsite of thrombin, the amino acid being N-terminally linked to a moiety which binds the S3 subsite of thrombin.
6. A formulation of any of claims 1 to 4 wherein YCO- is an optionally N-terminally protected dipeptide which binds to the S3 and S2 binding sites of thrombin.
7. A formulation of claim 6 wherein said dipeptide is N-terminally protected.
8. A formulation of claim 6 or claim 7 wherein Y comprises a P3 residue which has a side chain of formula (B):
-(CO)a-(CH2)b-Dc-Ce(E1)(E2)(E3) (B)
wherein
a is 0 or 1;
e is 1;
b is 0 or an integer such that (b e) is from 1 to 4;
c is 0 or 1;
D is O or S;
E1, E2 and E3 are each independently selected from -R15 and -J-R15, where J is a 5-6 membered ring and -R15 is selected from C1-C6 trialkylsilyl, -CN, -R13, -R12OR13, -R12COR13, -R12CO2R13, R12O2CR13, and one or two halogens, wherein R12 is (CH2)f– and R13 is -(CH2)gH wherein f and g are each independently from 0 to 10, provided that (f g) is 1, 2, 3 or 4.
Translation - Latvian PRASĪBAS
1. Parenterāla farmaceitiska formulācija, kura satur farmaceitiski pieņemamu borskābes bāzes pievienošanas sāls ar formulu (I):
kur
Y satur hidrofobu daļu, kurai, kopā ar aminoborskābes atlikumu
–NHCH(R9)-B(OH)2, piemīt afinitāte pret trombīna substrāta saistvietnēm; un
R9 ir taisna alkilgrupas ķēde ar vienu vai vairākiem iestarpinātiem ētera savienojumiem un kur kopējais skābekļa un oglekļa atomu skaits ir 3,4,5 vai 6 vai arī R9 ir –(CH2)m-W, kur m ir 2, 3, 4 vai 5 un W ir –OH vai halogēns (F, Cl, Br vai I),
un, kad YCO- ir neobligāti N-norobežoti aizsargāts dipeptīda atlikums, peptīdu savienojumi skābē tiek neobligāti un neatkarīgi N-aizvietoti ar C1-C13 hidrokarbilgrupu, kura var ietvert iekš ķēdes vai iekš gredzena slāpekli, skābekli vai sēru un var tikt aizvietota ar aizvietotāju, kas izvēlēts no halo, hidroksīd un triflormetila.
2. Prasības Nr. 1 formulācija, kur R9 alkoksialkilgrupa.
3. Prasības Nr. 1 un Nr. 2 formulācija, kur neviens peptīda savienojums skābē netiek aizvietots.
4. Prasības Nr. 1 un Nr. 2 formulācija, kur minētā C1-C13 hidrokarbilgrupa ir piesātināta C1-C6 hidrokarbilgrupa.
5. Jebkuras prasības no Nr. 1 līdz Nr. 4 formulācija, kur YCO- satur aminoskābi, kas saistās ar S2 trombīna apakšvietni, aminoskābei esot
N-norobežoti pievienotai tai daļai, kas saistās ar S3 trombīna apakšvietni.
6. Jebkuras prasības no Nr. 1 līdz Nr. 4 formulācija, kur YCO- ir neobligāti
N-norobežoti aizsargāts dipeptīds, kas saistās ar S3 un S2 trombīna saistvietnēm.
7. Prasības Nr. 6 formulācija, kur minētais dipeptīds ir N-norobežoti aizsargāts.
8. Prasības Nr. 6 vai Nr. 7 formulācija, kur Y satur P3 atlikumu, kuram ir sānķēde ar formulu (B):
-(CO)a-(CH2)b-Dc-Ce(E1)(E2)(E3) (B)
kur
a ir 0 vai 1;
e ir 1;
b ir 0 vai vesels skaitlis, lai (b e) būtu no 1 līdz 4;
c ir 0 vai 1;
D ir O vai S;
E1, E2 un E3 katrs ir atsevišķi izvēlēts no -R15 un -J-R15, kur J ir 5-6 locekļu gredzens un -R15 ir izvēlēts no C1-C6 trialkilsilīcija, -CN, -R13, -R12OR13, -R12COR13, -R12CO2R13, R12O2CR13, un viens vai divi halogēni, kur R12 ir (CH2)f– un R13 ir -(CH2)gH, kur f un g katrs ir atsevišķi no 0 līdz 10, ņemot vērā, ka (f g) ir 1, 2, 3 vai 4.
Russian to English: Genetic Investigation - Predicting the Development of Diseases General field: Science Detailed field: Genetics
Source text - Russian Цель генетического исследования – прогнозирование развития заболеваний
Молекулярно-генетические исследования включают в себя:
1. Выявление носительства мутаций, обуславливающих наиболее частые наследственные моногенные болезни.
2. Определение неблагоприятных вариантов генных полиморфизмов – маркеров предрасположенности к основным мультифакториальным заболеваниям.
3. Определение биологического родства.
4. Установление отцовства.
5.Генетическую экспертизу.
6. Определение генетической чувствительности к лекарственным препаратам.
7. Молекулярно-генетическое определение резус – принадлежности.
8. Анализ кариотипа.
Выполнение исследований
Обычно причиной полиморфизма генов являются точечные мутации – замены отдельных нуклеотидов в молекуле ДНК, что приводит к изменению свойств гена. Некоторые мутации неизбежно являются причиной генных болезней и проявляются уже в детстве (муковисцидоз, гемофилия, синдром Жильбера и т.д.), это так называемые моногенные б
олезни, другие не приводят к болезням, но являются фактором предрасположенности к определенным заболеваниям (злокачественные опухоли, сердечно-сосудистые, аллергические и другие заболевания). В этом случае для развития болезни необходимы определенные внешние условия – характер питания, поступление в организм токсинов и онкогенов и др. Эти болезни называются мультифакториальными.
Выполнение лабораторного исследования и составление заключения в МК ЦЭЛТ занимает 2-3 недели. Генетическое тестирование по заданному перечню мутаций/полиморфизмов проводится всего один раз. Результат исследования не меняется на протяжении всей жизни. Если выявлено носительство рецессивных мутаций, связанных с наследственными моногенными болезнями, пациентам требуется консультации врача-генетика в случае планирования рождения ребенка. Если обнаружены плохие варианты полиморфизмов, связанные с риском возникновения мультифакториальных болезней – это не является гарантией неизбежного развития заболевания. Как правило, речь идет только об увеличении риска тех или иных болезней. Важным является то, что человек должен знать не только о рисках для своего здоровья, но и о способах снижения этого риска.
Translation - English Aim of Genetic Investigation – Predicting the Development of Diseases
Genetic investigations identify mutations (DNA polymorphemes) that are hereditary factors of multifactorial diseases.
Molecular-genetic investigations include:
1. Carriage identification of mutations that cause the most common hereditary monogenic diseases.
2. Determination of the unfavourable types of gene polymorphisms – predisposition markers of the main multifactorial diseases.
3. Determination of biological relation.
4. Paternity establishment.
5. Genetic expertise.
6. Determination of genetic susceptibility to medications.
7. Molecural-genetic determination of Rhesus (Rh) factor.
8. Karyotype analysis.
Implementation of Investigation
In general, gene polymorphism is caused by point mutations – the substitution of some nucleotides in a DNA molecule, which leads to a change in the properties of a gene. Some mutations inevitably cause genetic diseases and manifest themselves during childhood (mucoviscoidosis, haemophilia, Guilbert syndrome, etc.) and are known as monogenic diseases; other mutations do not lead do diseases, yet are predispository factors for other specific diseases (malignant tumours, cardio-vascular, allergic and other diseases). In this case certain extraneous conditions are necessary for the disease to develop – the type of nutrition, the intake of toxins and oncogenes in the organism, etc. Such diseases are known as multifactorial diseases.
Implementation of a laboratory investigation and drawing up a conclusion at MC CELT (Multi-disciplinary Clinic Center of Endosurgery and Lithotripsy) takes 2-3 weeks. Genetic testing according to the given list of mutations/polymorphisms is only carried out once. The result of the investigation does not change throughout a person's lifetime. If the carriage of recessive mutations that are linked with hereditary monogenic diseases were identified, the patients require consultations of a doctor-geneticist in the case of planned pregnancy. If adverse types of polymorphisms that are linked with a risk of onset of multifactorial diseases were detected, it does not however guarantee an inevitable onset of a disease. Generally it only means a risk increase of the onset of some diseases. It is important for a person to be aware of both personal health risks and the ways to decrease these risks.
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Years of experience: 18. Registered at ProZ.com: Jan 2011.
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