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Carlos Antônio de Carvalho Fernandes
                                Med. Vet. PhD.
                           cacf@biotran.com.br




São Paulo - SP
07/04/2009
Uterine Involution in cattle
Reduction by 95% of the
                 weight (approx. 8-
                 9kg) in 20-25 days




                   ???
               How does it happen?


1. Through lochia (20%)
    Shedding of caruncles

2 – Absorption (80%)
    Similar to inflammatory process
Retrospective
Retrospective view on the use of
prostaglandins in post partum
  Started with the treatment of calving
  problems (since 1978)
  Later verified with the information that the
  treated animals apart from showing clinical
  improvement also returned earlier to
  reproductive activity (1987)
Efficacy of the treatment of placental retention with
oxytetracycline HCl with or without simultaneous
administration of cloprostenol (Fernandes, 1999)

                    Variable                               Oxytetracycline   Oxyt+ Cloprostenol
                                                                HCl
Number of animals
                                                                90                  90
Infection at 30d post partum (%)
                                                               44,4               42,2
Degree of uterine involution* (%)
                                                               1,92               2,43
Interval calving-to-conception (d)*
                                                               78,4               54,1
Breeding period (d)*
                                                              131,3              111,7
Services/conception
                                                               2,41               2,03
 * Significativo pelo teste de ‘t’ a 5% de probabilidade
Retrospectiva da utilização de
prostaglandinas no pós-parto
  Started with the treatment of calving
  problems (since 1978)
  Later verified with the information that the
  treated animals apart from showing clinical
  improvement also returned earlier to
  reproductive activity (1987)
  Relationship between uterine involution and
  resumption of ovarian activity (1993)
  Use in animals without calving problems
  (2002)
Effects of Ciosin® administered during post
partum in various scientific studies in
comparison to a control group
      Author      Number of   Reduction in              Breed
                   females    post calving
                               interval (d)
Fernandes, 2002     217           32,0        Holandês
Zanchet,2004                                  Holandês
                    159           38,7

Zanchet,2004                                  Jersey
                    227           32,5

Fernandes,2004                                Nelore (primíparas)
                    190           17,3

Fernandes,2004                                Nelore (multíparas)
                    295           12,2

Fernandes,2006                                Vacas mestiças
                    320           14,7

Silveira 2008        78           12,3        Bufalos
Uterine
involution absorption relies
  The process of
  on a mechanism similar to
  inflammation
  Chemical mediators involved are
  also similar
  Derivatives of arachidonic acid,
  principally prostaglandins are
  among the most important
  Take care when using anti-
  inflammatory drugs
Uterine size and involution speed
 according to the number of days post
 partum

                        More than 50% of the
                        involution takes place within
                        the 1st week
                           Higher production of PGF and
                           related substances
Uterine
 Size                      Increase in the number of
                           receptors for PGF and analogues




          1   5   10     15      20    25     30
                   Dayss Post partum
Effect of cloprostenol sodium administered post
partum in dairy cows and resumption of reproductive
activity (Fernandes et al., 2002ab)

  Treatment scheme in post partum animals

            Group     Treatment scheme

            Control   Administration of one dose of 2ml physiological
                      solution, intramuscularly, at 2 days post partum

                      Administration of 0.530mg cloprostenol (Ciosin®)
            Group 2   in a single dose, intramuscularly, at 2 days post
                      partum

                      Administration of 0.530mg cloprostenol (Ciosin®),
            Group 3   intramuscularly, at 2 days post partum. Second
                      dose administered at 3-5 days post the 1st dose
Degree of uterine involution, assessed through rectal palpation
at 30d post partum in different treatment groups (Fernandes et al.
                              2002)




                                                       Degree of Involution
                                                           1 – Palpation possible
                                                          only of the tips of
                                                          uterine horns
                                                           2. Palpation of more
                                                          than half of the uterine
                                                          body possible within
                                                          the abdominal cavity
                                                           3. More than half of
                                                          the uterus located in
                                                          the pelvic cavity


                                                   P<0,05 Between Control
                                                   and Ciosin 2x
Average incidence of puerperal uterine
infections in dairy cows treated with
cloprostenol sodium in post partum period
(Fernandes et al. 2002)



                                   Effect of PGF
                                   1. Mechanical – reduction
                                   of uterine volume and
                                   expulsion of the lochiae
                                   2. Direct effect of PGF on
                                   the activity of cells
                                   forming the uterine
                                   immune defense




                                P<0,05 Between Control
                                and Ciosin 2x
Number of services per conception in cows
treated with cloprostenol sodium post
partum (Fernandes et al. 2002)




                     P>0,05
Reproductive performance of cows
treated with cloprostenol sodium post
partum (Fernandes et al. 2002)




                               P<0,05 Between Goups 1
                               and 3
New results


 Defining the most opportune treatment time

 Dose and frequency of administration
Camargos e Fernandes (2009). data not published
Treatment scheme in post partum
animals

                         Group
     Group     No                               Treatment scheme
                       description

                                         2ml of physiological saline
Control      120    Control
                                         intramuscularly, two doses

                                         Two doses of 0.530mg
                    Cloprostenol – 1st   cloprostenol, intramuscularly,
Group 2      120
                    week                 during the first week pp, with
                                         interval of 2-3 days
                                         Two doses of 0.530mg
                    Cloprostenol – 3rd   cloprostenol, intramuscularly,
Group 3      120
                    week                 during the third week pp, with
                                         interval of 2-3 days
Efeitos do cloprostenol em diferentes períodos
no pós-parto de vacas leiteiras (Camargos e Fernandes,
                        2009)


Esquema de tratamento dos animais após o
parto
        GRUPO            N                 Descrição
        Controle        120             Sem tratamento
                                    Duas doses de 0,530mg de
                                Cloprostenol via intramuscular, na
    Clorp 2x – 1ª Sem   120
                                 1ª semana pós-parto, com 2 a 3
                                        dias de intervalo
                                    Duas doses de 0,530mg de
                                Cloprostenol via intramuscular, na
    Clorp 2x – 3ª Sem   120
                                 3ª semana pós-parto, com 2 a 3
                                        dias de intervalo
Effects of cloprostenol administered at different times
 during post partum period in dairy cows (Camargos e
                    Fernandes, 2009)




                              P<0,05 Between Control and 1st Week
Fernandes et. al. - A Hora Veterinária. , v.156, p.09 - 13,
2007.
Effect of different cloprostenol (Ciosin®) doses
administered in post partum in beef cows (Fernandes et
                          al, 2007)


Treatment scheme in post partum animals
                  Number of
Treatment group                          Treatment description
                   animals


    Control         130                      No treatment


                                 A single dose of 0.530mg cloprostenol
   Clopr 2ml        132           (Ciosin®), intramuscularly, within the
                                         first 2 days post calving
                                 A single dose of 1.060mg cloprostenol
                                  (Ciosin®), intramuscularly, within the
   Clopr 4ml        136                  first 2 days post calving
Average interval calving-to-1st AI, cumulative and in
  different production sites and treatment groups
    (Fernandes et al., 2007) (Fernandes et al., 2007)




                             P<0,05 Between Control and 2ml or 4ml
                             No Difference betweem 2ml and 4ml
Average breeding period, cumulative and in different
production sites and treatment groups (Fernandes et al.,
                         2007)




                                 P<0,05 Between Control and 2ml or 4ml
                                 No Difference betweem 2ml and 4ml
Pilot study – 20 animals
(Fernandes et al., 2009, data not published)


 Treatment scheme in post partum animals

 Treatment   Number of
                                    Treatment description
   group      animals

   Control       5                       No treatment

   Clopr1x       5           0.530mg cloprostenol as a single dose

                         0.530mg cloprostenol divided in two doses with
   Clopr2x       5
                                        a 24h interval

                         0.530mg cloprostenol divided into 4 doses with
   Clopr4x       5
                                         12h interval
Average interval calving-to-1st AI in different
production sites and treatment groups (Fernandes et al.,
                         2007)
Conclusões

Dosage and number of administrations

   Doubling of the dose does not always result in an
   improvement of results
     Saturation of existing PGF receptors
     Rapid metabolism (half life of 90min)
     Dividing of the dose into a higher number of
     administrations
     Obtain better results with the same total dose
“O sucesso nasce do querer. Sempre
que o homem aplicar a determinação e
a persistência para um objetivo, ele
vencerá os obstáculos, e, se não atingir
o alvo, pelo menos fará coisas
admiráveis”.
                                José de Alencar




                   Carlos Antônio de Carvalho Fernandes
                             Med. Vet. D.Sc.
                           cacf@biotran.com.br

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Palestra pgf ppartointerveting-alexei

  • 1. Carlos Antônio de Carvalho Fernandes Med. Vet. PhD. cacf@biotran.com.br São Paulo - SP 07/04/2009
  • 3. Reduction by 95% of the weight (approx. 8- 9kg) in 20-25 days ??? How does it happen? 1. Through lochia (20%) Shedding of caruncles 2 – Absorption (80%) Similar to inflammatory process
  • 5. Retrospective view on the use of prostaglandins in post partum Started with the treatment of calving problems (since 1978) Later verified with the information that the treated animals apart from showing clinical improvement also returned earlier to reproductive activity (1987)
  • 6. Efficacy of the treatment of placental retention with oxytetracycline HCl with or without simultaneous administration of cloprostenol (Fernandes, 1999) Variable Oxytetracycline Oxyt+ Cloprostenol HCl Number of animals 90 90 Infection at 30d post partum (%) 44,4 42,2 Degree of uterine involution* (%) 1,92 2,43 Interval calving-to-conception (d)* 78,4 54,1 Breeding period (d)* 131,3 111,7 Services/conception 2,41 2,03 * Significativo pelo teste de ‘t’ a 5% de probabilidade
  • 7. Retrospectiva da utilização de prostaglandinas no pós-parto Started with the treatment of calving problems (since 1978) Later verified with the information that the treated animals apart from showing clinical improvement also returned earlier to reproductive activity (1987) Relationship between uterine involution and resumption of ovarian activity (1993) Use in animals without calving problems (2002)
  • 8. Effects of Ciosin® administered during post partum in various scientific studies in comparison to a control group Author Number of Reduction in Breed females post calving interval (d) Fernandes, 2002 217 32,0 Holandês Zanchet,2004 Holandês 159 38,7 Zanchet,2004 Jersey 227 32,5 Fernandes,2004 Nelore (primíparas) 190 17,3 Fernandes,2004 Nelore (multíparas) 295 12,2 Fernandes,2006 Vacas mestiças 320 14,7 Silveira 2008 78 12,3 Bufalos
  • 9. Uterine involution absorption relies The process of on a mechanism similar to inflammation Chemical mediators involved are also similar Derivatives of arachidonic acid, principally prostaglandins are among the most important Take care when using anti- inflammatory drugs
  • 10. Uterine size and involution speed according to the number of days post partum More than 50% of the involution takes place within the 1st week Higher production of PGF and related substances Uterine Size Increase in the number of receptors for PGF and analogues 1 5 10 15 20 25 30 Dayss Post partum
  • 11. Effect of cloprostenol sodium administered post partum in dairy cows and resumption of reproductive activity (Fernandes et al., 2002ab) Treatment scheme in post partum animals Group Treatment scheme Control Administration of one dose of 2ml physiological solution, intramuscularly, at 2 days post partum Administration of 0.530mg cloprostenol (Ciosin®) Group 2 in a single dose, intramuscularly, at 2 days post partum Administration of 0.530mg cloprostenol (Ciosin®), Group 3 intramuscularly, at 2 days post partum. Second dose administered at 3-5 days post the 1st dose
  • 12. Degree of uterine involution, assessed through rectal palpation at 30d post partum in different treatment groups (Fernandes et al. 2002) Degree of Involution 1 – Palpation possible only of the tips of uterine horns 2. Palpation of more than half of the uterine body possible within the abdominal cavity 3. More than half of the uterus located in the pelvic cavity P<0,05 Between Control and Ciosin 2x
  • 13. Average incidence of puerperal uterine infections in dairy cows treated with cloprostenol sodium in post partum period (Fernandes et al. 2002) Effect of PGF 1. Mechanical – reduction of uterine volume and expulsion of the lochiae 2. Direct effect of PGF on the activity of cells forming the uterine immune defense P<0,05 Between Control and Ciosin 2x
  • 14. Number of services per conception in cows treated with cloprostenol sodium post partum (Fernandes et al. 2002) P>0,05
  • 15. Reproductive performance of cows treated with cloprostenol sodium post partum (Fernandes et al. 2002) P<0,05 Between Goups 1 and 3
  • 16. New results Defining the most opportune treatment time Dose and frequency of administration
  • 17. Camargos e Fernandes (2009). data not published
  • 18. Treatment scheme in post partum animals Group Group No Treatment scheme description 2ml of physiological saline Control 120 Control intramuscularly, two doses Two doses of 0.530mg Cloprostenol – 1st cloprostenol, intramuscularly, Group 2 120 week during the first week pp, with interval of 2-3 days Two doses of 0.530mg Cloprostenol – 3rd cloprostenol, intramuscularly, Group 3 120 week during the third week pp, with interval of 2-3 days
  • 19. Efeitos do cloprostenol em diferentes períodos no pós-parto de vacas leiteiras (Camargos e Fernandes, 2009) Esquema de tratamento dos animais após o parto GRUPO N Descrição Controle 120 Sem tratamento Duas doses de 0,530mg de Cloprostenol via intramuscular, na Clorp 2x – 1ª Sem 120 1ª semana pós-parto, com 2 a 3 dias de intervalo Duas doses de 0,530mg de Cloprostenol via intramuscular, na Clorp 2x – 3ª Sem 120 3ª semana pós-parto, com 2 a 3 dias de intervalo
  • 20. Effects of cloprostenol administered at different times during post partum period in dairy cows (Camargos e Fernandes, 2009) P<0,05 Between Control and 1st Week
  • 21. Fernandes et. al. - A Hora Veterinária. , v.156, p.09 - 13, 2007.
  • 22. Effect of different cloprostenol (Ciosin®) doses administered in post partum in beef cows (Fernandes et al, 2007) Treatment scheme in post partum animals Number of Treatment group Treatment description animals Control 130 No treatment A single dose of 0.530mg cloprostenol Clopr 2ml 132 (Ciosin®), intramuscularly, within the first 2 days post calving A single dose of 1.060mg cloprostenol (Ciosin®), intramuscularly, within the Clopr 4ml 136 first 2 days post calving
  • 23. Average interval calving-to-1st AI, cumulative and in different production sites and treatment groups (Fernandes et al., 2007) (Fernandes et al., 2007) P<0,05 Between Control and 2ml or 4ml No Difference betweem 2ml and 4ml
  • 24. Average breeding period, cumulative and in different production sites and treatment groups (Fernandes et al., 2007) P<0,05 Between Control and 2ml or 4ml No Difference betweem 2ml and 4ml
  • 25. Pilot study – 20 animals (Fernandes et al., 2009, data not published) Treatment scheme in post partum animals Treatment Number of Treatment description group animals Control 5 No treatment Clopr1x 5 0.530mg cloprostenol as a single dose 0.530mg cloprostenol divided in two doses with Clopr2x 5 a 24h interval 0.530mg cloprostenol divided into 4 doses with Clopr4x 5 12h interval
  • 26. Average interval calving-to-1st AI in different production sites and treatment groups (Fernandes et al., 2007)
  • 27. Conclusões Dosage and number of administrations Doubling of the dose does not always result in an improvement of results Saturation of existing PGF receptors Rapid metabolism (half life of 90min) Dividing of the dose into a higher number of administrations Obtain better results with the same total dose
  • 28. “O sucesso nasce do querer. Sempre que o homem aplicar a determinação e a persistência para um objetivo, ele vencerá os obstáculos, e, se não atingir o alvo, pelo menos fará coisas admiráveis”. José de Alencar Carlos Antônio de Carvalho Fernandes Med. Vet. D.Sc. cacf@biotran.com.br