����JFIFXX�����    $.' ",#(7),01444'9=82<.342  2!!22222222222222222222222222222222222222222222222222����"��4�� ���,�PG"Z_�4�˷����kjز�Z�,F+��_z�,�© �����zh6�٨�ic�fu���#ډb���_�N�?��wQ���5-�~�I���8����TK<5o�Iv-�����k�_U_�����~b�M��d����Ӝ�U�Hh��?]��E�w��Q���k�{��_}qFW7HTՑ��Y��F�?_�'ϔ��_�Ջt��=||I ��6�έ"�����D���/[�k�9���Y�8ds|\���Ҿp6�Ҵ���]��.����6�z<�v��@]�i%��$j��~�g��J>��no����pM[me�i$[����s�o�ᘨ�˸ nɜG-�ĨU�ycP�3.DB�li�;��hj���x7Z^�N�h������N3u{�:j�x�힞��#M&��jL P@_���� P��&��o8������9�����@Sz6�t7#O�ߋ �s}Yf�T���lmr����Z)'N��k�۞p����w\�Tȯ?�8`�O��i{wﭹW�[�r�� ��Q4F�׊���3m&L�=��h3����z~��#�\�l :�F,j@�� ʱ�wQT����8�"kJO���6�֚l����}���R�>ډK���]��y����&����p�}b��;N�1�m�r$�|��7�>e�@B�TM*-iH��g�D�)� E�m�|�ؘbҗ�a��Ҿ����t4���o���G��*oCN�rP���Q��@z,|?W[0�����:�n,jWiE��W��$~/�hp\��?��{(�0���+�Y8rΟ�+����>S-S����VN;�}�s?.����� w�9��˟<���Mq4�Wv'��{)0�1mB��V����W[�����8�/<� �%���wT^�5���b��)iM� pg�N�&ݝ��VO~�q���u���9� ����!��J27����$O-���! �:�%H��� ـ����y�ΠM=t{!S�� oK8������t<����è:a������[�����ա�H���~��w��Qz`�po�^ ����Q��n� �,uu�C�$ ^���,������8�#��:�6��e�|~���!�3�3.�\0��q��o�4`.|� ����y�Q�`~;�d�ׯ,��O�Zw�������`73�v�܋�<���Ȏ�� ـ4k��5�K�a�u�=9Yd��$>x�A�&�� j0� ���vF��� Y�|�y��� ~�6�@c��1vOp�Ig����4��l�OD���L����� R���c���j�_�uX6��3?nk��Wy�f;^*B� ��@�~a�`��Eu������+���6�L��.ü>��}y���}_�O�6�͐�:�YrG�X��kG�����l^w���~㒶sy��Iu�!� W ��X��N�7BV��O��!X�2����wvG�R�f�T#�����t�/?���%8�^�W�aT��G�cL�M���I��(J����1~�8�?aT ���]����AS�E��(��*E}� 2��#I/�׍qz��^t�̔���b�Yz4x���t�){ OH��+(E��A&�N�������XT��o��"�XC��'���)}�J�z�p� ��~5�}�^����+�6����w��c��Q�|Lp�d�H��}�(�.|����k��c4^�"�����Z?ȕ ��a<�L�!039C� �Eu�C�F�Ew�ç ;�n?�*o���B�8�bʝ���'#Rqf���M}7����]����s2tcS{�\icTx;�\��7K���P���ʇ Z O-��~��c>"��?�������P��E��O�8��@�8��G��Q�g�a�Վ���󁶠�䧘��_%#r�>�1�z�a��eb��qcPѵ��n���#L��� =��׀t� L�7�`��V���A{�C:�g���e@�w1 Xp3�c3�ġ����p��M"'-�@n4���fG��B3�DJ�8[Jo�ߐ���gK)ƛ��$���� ���8�3�����+���� �����6�ʻ���� ���S�kI�*KZlT _`���?��K����QK�d����B`�s}�>���`��*�>��,*@J�d�oF*����弝��O}�k��s��]��y�ߘ��c1G�V���<=�7��7����6�q�PT��tXԀ�!9*4�4Tހ3XΛex�46���Y��D ����� �BdemDa����\�_l,��G�/���֌7���Y�](�xTt^%�GE�����4�}bT���ڹ�����;Y)���B�Q��u��>J/J �⮶.�XԄ��j�ݳ�+E��d ��r�5�_D�1 ��o�� �B�x�΢�#���<��W�����8���R6�@g�M�.��� dr�D��>(otU��@x=��~v���2� ӣ�d�oBd��3�eO�6�㣷�����ݜ6��6Y��Qz`��S��{���\P�~z m5{J/L��1������<�e�ͅPu�b�]�ϔ���'������f�b� Zpw��c`"��i���BD@:)ִ�:�]��hv�E�w���T�l��P���"Ju�}��وV J��G6��. J/�Qgl߭�e�����@�z�Zev2u�)]կ�����7x���s�M�-<ɯ�c��r�v�����@��$�ޮ}lk���a���'����>x��O\�ZFu>�����ck#��&:��`�$�ai�>2Δ����l���oF[h��lE�ܺ�Πk:)���`�� $[6�����9�����kOw�\|���8}������ބ:��񶐕��I�A1/�=�2[�,�!��.}gN#�u����b��� ~��݊��}34q����d�E��Lc��$��"�[q�U�硬g^��%B �z���r�pJ�ru%v\h1Y�ne`ǥ:g���pQM~�^�Xi� ��`S�:V29.�P���V�?B�k�� AEvw%�_�9C�Q����wKekPؠ�\�;Io d�{ ߞo�c1eP����\� `����E=���@K<�Y���eڼ�J���w����{av�F�'�M�@/J��+9p���|]�����Iw &`��8���&M�hg��[�{��Xj��%��Ӓ�$��(����ʹN���<>�I���RY���K2�NPlL�ɀ)��&e����B+ь����( � �JTx���_?EZ� }@ 6�U���뙢ط�z��dWI�n` D����噥�[��uV��"�G&Ú����2g�}&m��?ċ�"����Om#��������� ��{�ON��"S�X��Ne��ysQ���@Fn��Vg���dX�~nj�]J�<�K]:��FW��b�������62�=��5f����JKw��bf�X�55��~J �%^����:�-�QIE��P��v�nZum� z � ~ə ���� ���ة����;�f��\v���g�8�1��f24;�V���ǔ�)����9���1\��c��v�/'Ƞ�w�������$�4�R-��t���� e�6�/�ġ �̕Ecy�J���u�B���<�W�ַ~�w[B1L۲�-JS΂�{���΃������A��20�c#��@ 0!1@AP"#2Q`$3V�%45a6�FRUq��� ����^7ׅ,$n�������+��F�`��2X'��0vM��p�L=������5��8������u�p~���.�`r�����\���O��,ư�0oS ��_�M�����l���4�kv\JSd���x���SW�<��Ae�IX����������$I���w�:S���y���›R��9�Q[���,�5�;�@]�%���u�@ *ro�lbI �� ��+���%m:�͇ZV�����u�̉����θau<�fc�.����{�4Ա� �Q����*�Sm��8\ujqs]{kN���)qO�y�_*dJ�b�7���yQqI&9�ԌK!�M}�R�;������S�T���1���i[U�ɵz�]��U)V�S6���3$K{�ߊ<�(� E]Զ[ǼENg�����'�\?#)Dkf��J���o��v���'�%ƞ�&K�u�!��b�35LX�Ϸ��63$K�a�;�9>,R��W��3�3� d�JeTYE.Mϧ��-�o�j3+y��y^�c�������VO�9NV\nd�1 ��!͕_)a�v;����թ�M�lWR1��)El��P;��yوÏ�u 3�k�5Pr6<�⒲l�!˞*��u־�n�!�l:����UNW ��%��Chx8vL'��X�@��*��)���̮��ˍ��� ���D-M�+J�U�kvK����+�x8��cY������?�Ԡ��~3mo��|�u@[XeY�C�\Kp�x8�oC�C�&����N�~3-H���� ��MX�s�u<`���~"WL��$8ξ��3���a�)|:@�m�\���^�`�@ҷ)�5p+��6���p�%i)P M���ngc�����#0Aruz���RL+xSS?���ʮ}()#�t��mˇ!��0}}y����<�e� �-ή�Ԩ��X������ MF���ԙ~l L.3���}�V뽺�v�����멬��Nl�)�2����^�Iq��a��M��qG��T�����c3#������3U�Ǎ���}��לS�|qa��ڃ�+���-��2�f����/��bz��ڐ�� �ݼ[2�ç����k�X�2�* �Z�d���J�G����M*9W���s{��w���T��x��y,�in�O�v��]���n����P�$�JB@=4�OTI�n��e�22a\����q�d���%�$��(���:���: /*�K[PR�fr\nڙdN���F�n�$�4�[�� U�zƶ����� �mʋ���,�ao�u 3�z� �x��Kn����\[��VFmbE;�_U��&V�Gg�]L�۪&#n%�$ɯ�dG���D�TI=�%+AB�Ru#��b4�1�»x�cs�YzڙJG��f��Il��d�eF'T� iA��T���uC�$����Y��H?����[!G`}���ͪ� �纤Hv\������j�Ex�K���!���OiƸ�Yj�+u-<���'q����uN�*�r\��+�]���<�wOZ.fp�ێ��,-*)V?j-kÊ#�`�r��dV����(�ݽBk�����G�ƛk�QmUڗe��Z���f}|����8�8��a���i��3'J�����~G_�^���d�8w������ R�`(�~�.��u���l�s+g�bv���W���lGc}��u���afE~1�Ue������Z�0�8�=e�� f@/�jqEKQQ�J��oN��J���W5~M>$6�Lt�;$ʳ{���^��6�{����v6���ķܰg�V�cnn �~z�x�«�,2�u�?cE+Ș�H؎�%�Za�)���X>uW�Tz�Nyo����s���FQƤ��$��*�&�LLXL)�1�" L��eO��ɟ�9=���:t��Z���c��Ž���Y?�ӭV�wv�~,Y��r�ۗ�|�y��GaF�����C�����.�+� ���v1���fήJ�����]�S��T��B��n5sW}y�$��~z�'�c ��8 ��� ,! �p��VN�S��N�N�q��y8z˱�A��4��*��'������2n<�s���^ǧ˭P�Jޮɏ�U�G�L�J�*#��<�V��t7�8����TĜ>��i}K%,���)[��z�21z ?�N�i�n1?T�I�R#��m-�����������������1����lA�`��fT5+��ܐ�c�q՝��ʐ��,���3�f2U�եmab��#ŠdQ�y>\��)�SLY����w#��.���ʑ�f��� ,"+�w�~�N�'�c�O�3F�������N<���)j��&��,-� �љ���֊�_�zS���TǦ����w�>��?�������n��U仆�V���e�����0���$�C�d���rP �m�׈e�Xm�Vu� �L��.�bֹ��� �[Դaզ���*��\y�8�Է:�Ez\�0�Kq�C b��̘��cө���Q��=0Y��s�N��S.���3.���O�o:���#���v7�[#߫ ��5�܎�L���Er4���9n��COWlG�^��0k�%<���ZB���aB_���������'=��{i�v�l�$�uC���mƎҝ{�c㱼�y]���W�i ��ߧc��m�H� m�"�"�����;Y�ߝ�Z�Ǔ�����:S#��|}�y�,/k�Ld� TA�(�AI$+I3��;Y*���Z��}|��ӧO��d�v��..#:n��f>�>���ȶI�TX��� 8��y����"d�R�|�)0���=���n4��6ⲑ�+��r<�O�܂~zh�z����7ܓ�HH�Ga롏���nCo�>������a ���~]���R���̲c?�6(�q�;5%� |�uj�~z8R=X��I�V=�|{v�Gj\gc��q����z�؋%M�ߍ����1y��#��@f^���^�>N�����#x#۹��6�Y~�?�dfPO��{��P�4��V��u1E1J �*|���%���JN��`eWu�zk M6���q t[�� ��g�G���v��WIG��u_ft����5�j�"�Y�:T��ɐ���*�;� e5���4����q$C��2d�}���� _S�L#m�Yp��O�.�C�;��c����Hi#֩%+) �Ӎ��ƲV���SYź��g |���tj��3�8���r|���V��1#;.SQ�A[���S������#���`n�+���$��$I �P\[�@�s��(�ED�z���P��])8�G#��0B��[ى��X�II�q<��9�~[Z멜�Z�⊔IWU&A>�P~�#��dp<�?����7���c��'~���5 ��+$���lx@�M�dm��n<=e�dyX��?{�|Aef ,|n3�<~z�ƃ�uۧ�����P��Y,�ӥQ�*g�#먙R�\���;T��i,��[9Qi歉����c>]9�� ��"�c��P�� �Md?٥��If�ت�u��k��/����F��9�c*9��Ǎ:�ØF���z�n*�@|I�ށ9����N3{'��[�'ͬ�Ҳ4��#}��!�V� Fu��,�,mTIk���v C�7v���B�6k�T9��1�*l� '~��ƞF��lU��'�M ����][ΩũJ_�{�i�I�n��$���L�� j��O�dx�����kza۪��#�E��Cl����x˘�o�����V���ɞ�ljr��)�/,�߬h�L��#��^��L�ф�,íMƁe�̩�NB�L�����iL����q�}��(��q��6IçJ$�W�E$��:������=#����(�K�B����zђ <��K(�N�۫K�w��^O{!����)�H���>x�������lx�?>Պ�+�>�W���,Ly!_�D���Ō�l���Q�!�[ �S����J��1��Ɛ�Y}��b,+�Lo�x�ɓ)����=�y�oh�@�꥟/��I��ѭ=��P�y9��� �ۍYӘ�e+�p�Jnϱ?V\SO%�(�t� ���=?MR�[Ș�����d�/ ��n�l��B�7j� ��!�;ӥ�/�[-���A�>�dN�sLj ��,ɪv��=1c�.SQ�O3�U���ƀ�ܽ�E����������̻��9G�ϷD�7(�}��Ävӌ\�y�_0[w ���<΍>����a_��[0+�L��F.�޺��f�>oN�T����q;���y\��bՃ��y�jH�<|q-eɏ�_?_9+P���Hp$�����[ux�K w�Mw��N�ی'$Y2�=��q���KB��P��~������Yul:�[<����F1�2�O���5=d����]Y�sw:���Ϯ���E��j,_Q��X��z`H1,#II ��d�wr��P˂@�ZJV����y$�\y�{}��^~���[:N����ߌ�U�������O��d�����ؾe��${p>G��3c���Ė�lʌ�� ת��[��`ϱ�-W����dg�I��ig2��� ��}s ��ؤ(%#sS@���~���3�X�nRG�~\jc3�v��ӍL��M[JB�T��s3}��j�Nʖ��W����;7��ç?=X�F=-�=����q�ߚ���#���='�c��7���ڑW�I(O+=:uxq�������������e2�zi+�kuG�R��������0�&e�n���iT^J����~\jy���p'dtG��s����O��3����9* �b#Ɋ�� p������[Bws�T�>d4�ۧs���nv�n���U���_�~,�v����ƜJ1��s�� �QIz��)�(lv8M���U=�;����56��G���s#�K���MP�=��LvyGd��}�VwWBF�'�à �?MH�U�g2�� ����!�p�7Q��j��ڴ����=��j�u��� Jn�A s���uM������e��Ɔ�Ҕ�!)'��8Ϣ�ٔ��ޝ(��Vp���צ֖d=�IC�J�Ǡ{q������kԭ�߸���i��@K����u�|�p=..�*+����x�����z[Aqġ#s2a�Ɗ���RR�)*HRsi�~�a &f��M��P����-K�L@��Z��Xy�'x�{}��Zm+���:�)�) IJ�-i�u���� ���ܒH��'�L(7�y�GӜq���� j��� 6ߌg1�g�o���,kر���tY�?W,���p���e���f�OQS��!K�۟cҒA�|ս�j�>��=⬒��˧L[�� �߿2JaB~R��u�:��Q�] �0H~���]�7��Ƽ�I���(}��cq '�ήET���q�?f�ab���ӥvr� �)o��-Q��_'����ᴎo��K������;��V���o��%���~OK ����*��b�f:���-ťIR��`B�5!RB@���ï�� �u �̯e\�_U�_������� g�ES��3�������QT��a����x����U<~�c?�*�#]�MW,[8O�a�x��]�1bC|踤�P��lw5V%�)�{t�<��d��5���0i�XSU��m:��Z�┵�i�"��1�^B�-��P�hJ��&)O��*�D��c�W��vM��)����}���P��ܗ-q����\mmζZ-l@�}��a��E�6��F�@��&Sg@���ݚ�M����� ȹ 4����#p�\H����dYDo�H���"��\��..R�B�H�z_�/5˘����6��KhJR��P�mƶi�m���3�,#c�co��q�a)*Pt����R�m�k�7x�D�E�\Y�閣_X�<���~�)���c[[�BP����6�Yq���S��0����%_����;��Àv�~�| VS؇ ��'O0��F0��\���U�-�d@�����7�SJ*z��3n��y��P����O���������m�~�P�3|Y��ʉr#�C�<�G~�.,! ���bqx���h~0=��!ǫ�jy����l�O,�[B��~��|9��ٱ����Xly�#�i�B��g%�S��������tˋ���e���ې��\[d�t)��.+u�|1 ������#�~Oj����hS�%��i.�~X���I�H�m��0n���c�1uE�q��cF�RF�o���7� �O�ꮧ� ���ۛ{��ʛi5�rw?׌#Qn�TW��~?y$��m\�\o����%W� ?=>S�N@�� �Ʈ���R����N�)�r"C�:��:����� �����#��qb��Y�. �6[��2K����2u�Ǧ�HYR��Q�MV��� �G�$��Q+.>�����nNH��q�^��� ����q��mM��V��D�+�-�#*�U�̒ ���p욳��u:�������IB���m���PV@O���r[b= �� ��1U�E��_Nm�yKbN�O���U�}�the�`�|6֮P>�\2�P�V���I�D�i�P�O;�9�r�mAHG�W�S]��J*�_�G��+kP�2����Ka�Z���H�'K�x�W�MZ%�O�YD�Rc+o��?�q��Ghm��d�S�oh�\�D�|:W������UA�Qc yT�q������~^�H��/��#p�CZ���T�I�1�ӏT����4��"�ČZ�����}��`w�#�*,ʹ�� ��0�i��課�Om�*�da��^gJ݅{���l�e9uF#T�ֲ��̲�ٞC"�q���ߍ ոޑ�o#�XZTp����@ o�8��(jd��xw�]�,f���`~�|,s��^����f�1���t��|��m�򸄭/ctr��5s��7�9Q�4�H1꠲BB@l9@���C�����+�wp�xu�£Yc�9��?`@#�o�mH�s2��)�=��2�.�l����jg�9$�Y�S�%*L������R�Y������7Z���,*=�䷘$�������arm�o�ϰ���UW.|�r�uf����IGw�t����Zwo��~5 ��YյhO+=8fF�)�W�7�L9lM�̘·Y���֘YLf�큹�pRF���99.A �"wz��=E\Z���'a� 2��Ǚ�#;�'}�G���*��l��^"q��+2FQ� hj��kŦ��${���ޮ-�T�٭cf�|�3#~�RJ����t��$b�(R��(����r���dx� >U b�&9,>���%E\� Ά�e�$��'�q't��*�א���ެ�b��-|d���SB�O�O��$�R+�H�)�܎�K��1m`;�J�2�Y~9��O�g8=vqD`K[�F)k�[���1m޼c��n���]s�k�z$@��)!I �x՝"v��9=�ZA=`Ɠi �:�E��)`7��vI��}d�YI�_ �o�:ob���o ���3Q��&D&�2=�� �Ά��;>�h����y.*ⅥS������Ӭ�+q&����j|UƧ����}���J0��WW< ۋS�)jQR�j���Ư��rN)�Gű�4Ѷ(�S)Ǣ�8��i��W52���No˓� ۍ%�5brOn�L�;�n��\G����=�^U�dI���8$�&���h��'���+�(������cȁ߫k�l��S^���cƗjԌE�ꭔ��gF���Ȓ��@���}O���*;e�v�WV���YJ\�]X'5��ղ�k�F��b 6R�o՜m��i N�i����>J����?��lPm�U��}>_Z&�KK��q�r��I�D�Չ~�q�3fL�:S�e>���E���-G���{L�6p�e,8��������QI��h��a�Xa��U�A'���ʂ���s�+טIjP�-��y�8ۈZ?J$��W�P� ��R�s�]��|�l(�ԓ��sƊi��o(��S0��Y� 8�T97.�����WiL��c�~�dxc�E|�2!�X�K�Ƙਫ਼�$((�6�~|d9u+�qd�^3�89��Y�6L�.I�����?���iI�q���9�)O/뚅����O���X��X�V��ZF[�یgQ�L��K1���RҖr@v�#��X�l��F���Нy�S�8�7�kF!A��sM���^rkp�jP�DyS$N���q��nxҍ!U�f�!eh�i�2�m���`�Y�I�9r�6� �TF���C}/�y�^���Η���5d�'��9A-��J��>{�_l+�`��A���[�'��յ�ϛ#w:݅�%��X�}�&�PSt�Q�"�-��\縵�/����$Ɨh�Xb�*�y��BS����;W�ջ_mc�����vt?2}1�;qS�d�d~u:2k5�2�R�~�z+|HE!)�Ǟl��7`��0�<�,�2*���Hl-��x�^����'_TV�gZA�'j� ^�2Ϊ��N7t�����?w�� �x1��f��Iz�C-Ȗ��K�^q�;���-W�DvT�7��8�Z�������� hK�(P:��Q- �8�n�Z���܃e貾�<�1�YT<�,�����"�6{/ �?�͟��|1�:�#g��W�>$����d��J��d�B��=��jf[��%rE^��il:��B���x���Sּ�1հ��,�=��*�7 fcG��#q� �eh?��2�7�����,�!7x��6�n�LC�4x��},Geǝ�tC.��vS �F�43��zz\��;QYC,6����~;RYS/6���|2���5���v��T��i����������mlv��������&� �nRh^ejR�LG�f���? �ۉҬܦƩ��|��Ȱ����>3����!v��i�ʯ�>�v��オ�X3e���_1z�Kȗ\<������!�8���V��]��?b�k41�Re��T�q��mz��TiOʦ�Z��Xq���L������q"+���2ۨ��8}�&N7XU7Ap�d�X��~�׿��&4e�o�F��� �H����O���č�c�� 懴�6���͉��+)��v;j��ݷ�� �UV�� i��� j���Y9GdÒJ1��詞�����V?h��l����l�cGs�ځ�������y�Ac�����\V3�? �� ܙg�>qH�S,�E�W�[�㺨�uch�⍸�O�}���a��>�q�6�n6����N6�q������N ! 1AQaq�0@����"2BRb�#Pr���3C`��Scst���$4D���%Td�� ?���N����a��3��m���C���w��������xA�m�q�m���m������$����4n淿t'��C"w��zU=D�\R+w�p+Y�T�&�պ@��ƃ��3ޯ?�Aﶂ��aŘ���@-�����Q�=���9D��ռ�ѻ@��M�V��P��܅�G5�f�Y<�u=,EC)�<�Fy'�"�&�չ�X~f��l�KԆV��?�� �W�N����=(� �;���{�r����ٌ�Y���h{�١������jW����P���Tc�����X�K�r��}���w�R��%��?���E��m�� �Y�q|����\lEE4���r���}�lsI�Y������f�$�=�d�yO����p�����yBj8jU�o�/�S��?�U��*������ˍ�0������u�q�m [�?f����a�� )Q�>����6#������� ?����0UQ����,IX���(6ڵ[�DI�MNލ�c&���υ�j\��X�R|,4��� j������T�hA�e��^���d���b<����n�� �즇�=!���3�^�`j�h�ȓr��jẕ�c�,ٞX����-����a�ﶔ���#�$��]w�O��Ӫ�1y%��L�Y<�wg#�ǝ�̗`�x�xa�t�w��»1���o7o5��>�m뭛C���Uƃߜ}�C���y1Xνm�F8�jI���]����H���ۺиE@I�i;r�8ӭ����V�F�Շ| ��&?�3|x�B�MuS�Ge�=Ӕ�#BE5G�����Y!z��_e��q�р/W>|-�Ci߇�t�1ޯќd�R3�u��g�=0 5��[?�#͏��q�cf���H��{ ?u�=?�?ǯ���}Z��z���hmΔ�BFTW�����<�q�(v� ��!��z���iW]*�J�V�z��gX֧A�q�&��/w���u�gYӘa���; �i=����g:��?2�dž6�ى�k�4�>�Pxs����}������G�9��3 ���)gG�R<>r h�$��'nc�h�P��Bj��J�ҧH� -��N1���N��?��~��}-q!=��_2hc�M��l�vY%UE�@|�v����M2�.Y[|y�"Eï��K�ZF,�ɯ?,q�?v�M 80jx�"�;�9vk�����+ ֧�� �ȺU��?�%�vcV��mA�6��Qg^M����A}�3�nl� QRN�l8�kkn�'�����(��M�7m9و�q���%ޟ���*h$Zk"��$�9��: �?U8�Sl��,,|ɒ��xH(ѷ����Gn�/Q�4�P��G�%��Ա8�N��!� �&�7�;���eKM7�4��9R/%����l�c>�x;������>��C�:�����t��h?aKX�bhe�ᜋ^�$�Iհ �hr7%F$�E��Fd���t��5���+�(M6�t����Ü�UU|zW�=a�Ts�Tg������dqP�Q����b'�m���1{|Y����X�N��b �P~��F^F:����k6�"�j!�� �I�r�`��1&�-$�Bevk:y���#yw��I0��x��=D�4��tU���P�ZH��ڠ底taP��6����b>�xa����Q�#� WeF��ŮNj�p�J* mQ�N����*I�-*�ȩ�F�g�3 �5��V�ʊ�ɮ�a��5F���O@{���NX��?����H�]3��1�Ri_u��������ѕ�� ����0��� F��~��:60�p�͈�S��qX#a�5>���`�o&+�<2�D����: �������ڝ�$�nP���*)�N�|y�Ej�F�5ټ�e���ihy�Z �>���k�bH�a�v��h�-#���!�Po=@k̆IEN��@��}Ll?j�O������߭�ʞ���Q|A07x���wt!xf���I2?Z��<ץ�T���cU�j��]��陎Ltl �}5�ϓ��$�,��O�mˊ�;�@O��jE��j(�ا,��LX���LO���Ц�90�O �.����a��nA���7������j4 ��W��_ٓ���zW�jcB������y՗+EM�)d���N�g6�y1_x��p�$Lv:��9�"z��p���ʙ$��^��JԼ*�ϭ����o���=x�Lj�6�J��u82�A�H�3$�ٕ@�=Vv�]�'�qEz�;I˼��)��=��ɯ���x �/�W(V���p�����$ �m�������u�����񶤑Oqˎ�T����r��㠚x�sr�GC��byp�G��1ߠ�w e�8�$⿄����/�M{*}��W�]˷.�CK\�ުx���/$�WPw���r� |i���&�}�{�X� �>��$-��l���?-z���g����lΆ���(F���h�vS*���b���߲ڡn,|)mrH[���a�3�ר�[1��3o_�U�3�TC�$��(�=�)0�kgP���� ��u�^=��4 �WYCҸ:��vQ�ר�X�à��tk�m,�t*��^�,�}D*� �"(�I��9R����>`�`��[~Q]�#af��i6l��8���6�:,s�s�N6�j"�A4���IuQ��6E,�GnH��zS�HO�uk�5$�I�4��ؤ�Q9�@��C����wp�BGv[]�u�Ov���0I4���\��y�����Q�Ѹ��~>Z��8�T��a��q�ޣ;z��a���/��S��I:�ܫ_�|������>=Z����8:�S��U�I�J��"IY���8%b8���H��:�QO�6�;7�I�S��J��ҌAά3��>c���E+&jf$eC+�z�;��V����� �r���ʺ������my�e���aQ�f&��6�ND��.:��NT�vm�<- u���ǝ\MvZY�N�NT��-A�>jr!S��n�O 1�3�Ns�%�3D@���`������ܟ 1�^c<���� �a�ɽ�̲�Xë#�w�|y�cW�=�9I*H8�p�^(4���՗�k��arOcW�tO�\�ƍR��8����'�K���I�Q�����?5�>[�}��yU�ײ -h��=��% q�ThG�2�)���"ו3]�!kB��*p�FDl�A���,�eEi�H�f�Ps�����5�H:�Փ~�H�0Dت�D�I����h�F3�������c��2���E��9�H��5�zԑ�ʚ�i�X�=:m�xg�hd(�v����׊�9iS��O��d@0ڽ���:�p�5�h-��t�&���X�q�ӕ,��ie�|���7A�2���O%P��E��htj��Y1��w�Ѓ!����  ���� ࢽ��My�7�\�a�@�ţ�J �4�Ȼ�F�@o�̒?4�wx��)��]�P��~�����u�����5�����7X ��9��^ܩ�U;Iꭆ 5 �������eK2�7(�{|��Y׎ �V��\"���Z�1� Z�����}��(�Ǝ"�1S���_�vE30>���p;� ΝD��%x�W�?W?v����o�^V�i�d��r[��/&>�~`�9Wh��y�;���R��� ;;ɮT��?����r$�g1�K����A��C��c��K��l:�'��3 c�ﳯ*"t8�~l��)���m��+U,z��`(�>yJ�?����h>��]��v��ЍG*�{`��;y]��I�T� ;c��NU�fo¾h���/$���|NS���1�S�"�H��V���T���4��uhǜ�]�v;���5�͠x��'C\�SBpl���h}�N����� A�Bx���%��ޭ�l��/����T��w�ʽ]D�=����K���ž�r㻠l4�S�O?=�k �M:� ��c�C�a�#ha���)�ѐxc�s���gP�iG��{+���x���Q���I= �� z��ԫ+ �8"�k�ñ�j=|����c ��y��CF��/��*9ж�h{ �?4�o� ��k�m�Q�N�x��;�Y��4膚�a�w?�6�>e]�����Q�r�:����g�,i"�����ԩA�*M�<�G��b�if��l^M��5� �Ҩ�{����6J��ZJ�����P�*�����Y���ݛu�_4�9�I8�7���������,^ToR���m4�H��?�N�S�ѕw��/S��甍�@�9H�S�T��t�ƻ���ʒU��*{Xs�@����f�����֒Li�K{H�w^���������Ϥm�tq���s� ���ք��f:��o~s��g�r��ט� �S�ѱC�e]�x���a��) ���(b-$(�j>�7q�B?ӕ�F��hV25r[7 Y� }L�R��}����*sg+��x�r�2�U=�*'WS��ZDW]�WǞ�<��叓���{�$�9Ou4��y�90-�1�'*D`�c�^o?(�9��u���ݐ��'PI&� f�Jݮ�������:wS����jfP1F:X �H�9dԯ���˝[�_54 �}*;@�ܨ�� ð�yn�T���?�ןd�#���4rG�ͨ��H�1�|-#���Mr�S3��G�3�����)�.᧏3v�z֑��r����$G"�`j �1t��x0<Ɔ�Wh6�y�6��,œ�Ga��gA����y��b��)��h�D��ß�_�m��ü �gG;��e�v��ݝ�nQ� ��C����-�*��o���y�a��M��I�>�<���]obD��"�:���G�A��-\%LT�8���c�)��+y76���o�Q�#*{�(F�⽕�y����=���rW�\p���۩�c���A���^e6��K������ʐ�cVf5$�'->���ՉN"���F�"�UQ@�f��Gb~��#�&�M=��8�ט�JNu9��D��[̤�s�o�~������ G��9T�tW^g5y$b��Y'��س�Ǵ�=��U-2 #�MC�t(�i� �lj�@Q 5�̣i�*�O����s�x�K�f��}\��M{E�V�{�υ��Ƈ�����);�H����I��fe�Lȣr�2��>��W�I�Ȃ6������i��k�� �5�YOxȺ����>��Y�f5'��|��H+��98pj�n�.O�y�������jY��~��i�w'������l�;�s�2��Y��:'lg�ꥴ)o#'Sa�a�K��Z� �m��}�`169�n���"���x��I ��*+� }F<��cГ���F�P�������ֹ*�PqX�x۩��,� ��N�� �4<-����%����:��7����W���u�`����� $�?�I��&����o��o��`v�>��P��"��l���4��5'�Z�gE���8���?��[�X�7(��.Q�-��*���ތL@̲����v��.5���[��=�t\+�CNܛ��,g�SQnH����}*F�G16���&:�t��4ُ"A��̣��$�b �|����#rs��a�����T�� ]�<�j��BS�('$�ɻ� �wP;�/�n��?�ݜ��x�F��yUn�~mL*-�������Xf�wd^�a�}��f�,=t�׵i�.2/wpN�Ep8�OР���•��R�FJ� 55TZ��T �ɭ�<��]��/�0�r�@�f��V��V����Nz�G��^���7hZi����k��3�,kN�e|�vg�1{9]_i��X5y7� 8e]�U����'�-2,���e"����]ot�I��Y_��n�(JҼ��1�O ]bXc���Nu�No��pS���Q_���_�?i�~�x h5d'�(qw52] ��'ޤ�q��o1�R!���`ywy�A4u���h<קy���\[~�4�\ X�Wt/� 6�����n�F�a8��f���z �3$�t(���q��q�x��^�XWeN'p<-v�!�{�(>ӽDP7��ո0�y)�e$ٕv�Ih'Q�EA�m*�H��RI��=:��� ���4牢) �%_iN�ݧ�l]� �Nt���G��H�L��� ɱ�g<���1V�,�J~�ٹ�"K��Q�� 9�HS�9�?@��k����r�;we݁�]I�!{ �@�G�[�"��`���J:�n]�{�cA�E����V��ʆ���#��U9�6����j�#Y�m\��q�e4h�B�7��C�������d<�?J����1g:ٳ���=Y���D�p�ц� ׈ǔ��1�]26؜oS�'��9�V�FVu�P�h�9�xc�oq�X��p�o�5��Ա5$�9W�V(�[Ak�aY錎qf;�'�[�|���b�6�Ck��)��#a#a˙��8���=äh�4��2��C��4tm^ �n'c���]GQ$[Wҿ��i���vN�{Fu ��1�gx��1┷���N�m��{j-,��x�� Ūm�ЧS�[�s���Gna���䑴�� x�p 8<������97�Q���ϴ�v�aϚG��Rt�Һ׈�f^\r��WH�JU�7Z���y)�vg=����n��4�_)y��D'y�6�]�c�5̪�\� �PF�k����&�c;��cq�$~T�7j ���nç]�<�g ":�to�t}�159�<�/�8������m�b�K#g'I'.W�����6��I/��>v��\�MN��g���m�A�yQL�4u�Lj�j9��#44�t��l^�}L����n��R��!��t��±]��r��h6ٍ>�yҏ�N��fU�� ���� Fm@�8}�/u��jb9������he:A�y�ծw��GpΧh�5����l}�3p468��)U��d��c����;Us/�֔�YX�1�O2��uq�s��`hwg�r~�{ R��mhN��؎*q 42�*th��>�#���E����#��Hv�O����q�}�����6�e��\�,Wk�#���X��b>��p}�դ��3���T5��†��6��[��@�P�y*n��|'f�֧>�lư΂�̺����SU�'*�q�p�_S�����M�� '��c�6�����m�� ySʨ;M��r���Ƌ�m�Kxo,���Gm�P��A�G�:��i��w�9�}M(�^�V��$ǒ�ѽ�9���|���� �a����J�SQ�a���r�B;����}���ٻ֢�2�%U���c�#�g���N�a�ݕ�'�v�[�OY'��3L�3�;,p�]@�S��{ls��X�'���c�jw�k'a�.��}�}&�� �dP�*�bK=ɍ!����;3n�gΊU�ߴmt�'*{,=SzfD� A��ko~�G�aoq�_mi}#�m�������P�Xhύ����mxǍ�΂���巿zf��Q���c���|kc�����?���W��Y�$���_Lv����l߶��c���`?����l�j�ݲˏ!V��6����U�Ђ(A���4y)H���p�Z_�x��>���e��R��$�/�`^'3qˏ�-&Q�=?��CFVR �D�fV�9��{�8g�������n�h�(P"��6�[�D���< E�����~0<@�`�G�6����Hг�cc�� �c�K.5��D��d�B���`?�XQ��2��ٿyqo&+�1^� DW�0�ꊩ���G�#��Q�nL3��c���������/��x ��1�1[y�x�პCW��C�c�UĨ80�m�e�4.{�m��u���I=��f�����0QRls9���f���������9���~f�����Ǩ��a�"@�8���ȁ�Q����#c�ic������G��$���G���r/$W�(��W���V�"��m�7�[m�A�m����bo��D� j����۳� l���^�k�h׽����� ��#� iXn�v��eT�k�a�^Y�4�BN��ĕ��0 !01@Q"2AaPq3BR������?���@4�Q�����T3,���㺠�W�[=JK�Ϟ���2�r^7��vc�:�9 �E�ߴ�w�S#d���Ix��u��:��Hp��9E!�� V 2;73|F��9Y���*ʬ�F��D����u&���y؟��^EA��A��(ɩ���^��GV:ݜDy�`��Jr29ܾ�㝉��[���E;Fzx��YG��U�e�Y�C���� ����v-tx����I�sם�Ę�q��Eb�+P\ :>�i�C'�;�����k|z�رn�y]�#ǿb��Q��������w�����(�r|ӹs��[�D��2v-%��@;�8<a���[\o[ϧw��I!��*0�krs)�[�J9^��ʜ��p1)� "��/_>��o��<1����A�E�y^�C��`�x1'ܣn�p��s`l���fQ��):�l����b>�Me�jH^?�kl3(�z:���1ŠK&?Q�~�{�ٺ�h�y���/�[��V�|6��}�KbX����mn[-��7�5q�94�������dm���c^���h� X��5��<�eޘ>G���-�}�دB�ޟ� ��|�rt�M��V+�]�c?�-#ڛ��^ǂ}���Lkr���O��u�>�-D�ry� D?:ޞ�U��ǜ�7�V��?瓮�"�#���r��չģVR;�n���/_� ؉v�ݶe5d�b9��/O��009�G���5n�W����JpA�*�r9�>�1��.[t���s�F���nQ� V 77R�]�ɫ8����_0<՜�IF�u(v��4��F�k�3��E)��N:��yڮe��P�`�1}�$WS��J�SQ�N�j�ٺ��޵�#l���ј(�5=��5�lǏmoW�v-�1����v,W�mn��߀$x�<����v�j(����c]��@#��1������Ǔ���o'��u+����;G�#�޸��v-lη��/(`i⣍Pm^���ԯ̾9Z��F��������n��1��� ��]�[��)�'������:�֪�W��FC����� �B9،!?���]��V��A�Վ�M��b�w��G F>_DȬ0¤�#�QR�[V��kz���m�w�"��9ZG�7'[��=�Q����j8R?�zf�\a�=��O�U����*oB�A�|G���2�54 �p��.w7� �� ��&������ξxGHp� B%��$g�����t�Џ򤵍z���HN�u�Я�-�'4��0��;_��3 !01"@AQa2Pq#3BR������?��ʩca��en��^��8���<�u#��m*08r��y�N"�<�Ѳ0��@\�p��� �����Kv�D��J8�Fҽ� �f�Y��-m�ybX�NP����}�!*8t(�OqѢ��Q�wW�K��ZD��Δ^e��!� ��B�K��p~�����e*l}z#9ң�k���q#�Ft�o��S�R����-�w�!�S���Ӥß|M�l޶V��!eˈ�8Y���c�ЮM2��tk���� ������J�fS����Ö*i/2�����n]�k�\���|4yX�8��U�P.���Ы[���l��@"�t�<������5�lF���vU�����W��W��;�b�cД^6[#7@vU�xgZv��F�6��Q,K�v��� �+Ъ��n��Ǣ��Ft���8��0��c�@�!�Zq s�v�t�;#](B��-�nῃ~���3g������5�J�%���O������n�kB�ĺ�.r��+���#�N$?�q�/�s�6��p��a����a��J/��M�8��6�ܰ"�*������ɗud"\w���aT(����[��F��U՛����RT�b���n�*��6���O��SJ�.�ij<�v�MT��R\c��5l�sZB>F��<7�;EA��{��E���Ö��1U/�#��d1�a�n.1ě����0�ʾR�h��|�R��Ao�3�m3 ��%�� ���28Q� ��y��φ���H�To�7�lW>����#i`�q���c����a��� �m,B�-j����݋�'mR1Ήt�>��V��p���s�0IbI�C.���1R�ea�����]H�6����������4B>��o��](��$B���m�����a�!=��?�B� K�Ǿ+�Ծ"�n���K��*��+��[T#�{E�J�S����Q�����s�5�:�U�\wĐ�f�3����܆&�)����I���Ԇw��E T�lrTf6Q|R�h:��[K�� �z��c֧�G�C��%\��_�a�84��HcO�bi��ؖV��7H �)*ģK~Xhչ0��4?�0��� �E<���}3���#���u�?�� ��|g�S�6ꊤ�|�I#Hڛ� �ա��w�X��9��7���Ŀ%�SL��y6č��|�F�a 8���b��$�sק�h���b9RAu7�˨p�Č�_\*w��묦��F ����4D~�f����|(�"m���NK��i�S�>�$d7SlA��/�²����SL��|6N�}���S�˯���g��]6��; �#�.��<���q'Q�1|KQ$�����񛩶"�$r�b:���N8�w@��8$�� �AjfG|~�9F ���Y��ʺ��Bwؒ������M:I岎�G��`s�YV5����6��A �b:�W���G�q%l�����F��H���7�������Fsv7��k�� 403WebShell
403Webshell
Server IP : 172.67.215.126  /  Your IP : 172.69.214.219
Web Server : Apache/2.4.52 (Ubuntu)
System : Linux ip-172-31-19-221 6.8.0-1029-aws #31~22.04.1-Ubuntu SMP Thu Apr 24 21:16:18 UTC 2025 x86_64
User : www-data ( 33)
PHP Version : 8.1.28
Disable Function : NONE
MySQL : OFF  |  cURL : ON  |  WGET : ON  |  Perl : ON  |  Python : OFF  |  Sudo : ON  |  Pkexec : ON
Directory :  /efsdata/scitechnol.com/httpdocs/submission/uploads/

Upload File :
current_dir [ Writeable ] document_root [ Writeable ]

 

Command :


[ Back ]     

Current File : /efsdata/scitechnol.com/httpdocs/submission/uploads/280-0-Manuscript-2013-01-03.doc
��ࡱ�>��	ux����t�������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������_�)��0�bjbj,E,E	:�N/N/�I������������������������<�_$���������~#�#�#�#�#�#�#$&��(`�#u�X��XX�#�����$�!�!�!X\����~#�!X~#�!�!�!�������8���������!j#/$0_$�!+*~ �+*�!�!+*��!���'^�!�L������#�#!����_$XXXX��������������������������������������������������������������������+*���������� �:	)Histopathological evaluation of supportive effect of vitamin C on testes following long-term administration of copper sulfate in mice



Sakhaee, E.1, Abshenas, J.1, Kheirandish, R.2, Azari, O.1, Karamshahi, A.3

1 Department of Clinical Sciences, School of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran
2 Department of Pathobiology, School of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran
3 Student of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran



Abstract:
This study was set to investigate whether the adverse effects of long-term copper (Cu) consumption on testicular tissue could be prevented by vitamin C administration. Thirty-six sexually mature male NMRI mice were randomly divided into three groups of 12 animals. The first group (group Cu) which is treated by gavage with copper sulfate at a dose of 200 mgkg"1day"1 (0.2 ml) and 0.1 ml of distilled water daily via IP injection for 6 weeks, the treatment group (group Cu + Vit C) which is treated by gavage with copper sulfate at a dose of 200 mgkg"1day"1 (0.2 ml) and received 10 mgkg"1day"1 (0.1 ml) vitamin C by IP injection, and the control group (group C) which received the same volume of distilled water by gavage and IP injection during experimental period. Vitamin C can be one of the suitable choices for preventive therapeutic effects and/or improvement in testicular tissue after Copper toxicosis
 

Keywords: Copper poisoning, Vitamin C, Testes, Histopathology, Mice


Introduction:
Copper is an essential trace element that is widely distributed in animal tissues [1, 2]. Copper sulfate is the most common copper salt; however, other important copper salts include carbonate, cyanide, oxide, and sulfide [3]. Copper can be absorbed into the systemic circulation from the gastrointestinal tract, the lungs, and skin [3]. The gastrointestinal absorption of copper is influenced by a number of factors, including its chemical form: soluble copper compounds (oxides, hydroxides, citrates, and sulfate) are readily absorbed but water-insoluble compounds (sulfides) are poorly absorbed [4]. 
Soluble copper salts in high concentrations are protein coagulants. The ingestion of large quantities is associated with intense irritation of the alimentary mucosa and profound shock. Severe intravascular hemolysis occurs if the animal survives long enough. When excessive amounts of copper are injected the response is rapid and animals begin to die the next day and with a peak of mortality about the third day after dosing. Early deaths appear to be due to severe hepatic insufficiency and later deaths to renal failure due to tubular necrosis.  The frequent ingestion of small amounts produces no ill-effects while copper accumulates in the liver. When maximum hepatic levels are reached after periods of exposure often as long as 6 months, the copper is released into the bloodstream and the animal dies of acute intravascular hemolysis. One of the dangers of cumulative copper poisoning is that the animal shows normal health until the hemolytic crisis, when it becomes acutely ill and dies very quickly. Death is ascribed to acute anemia and hemoglobinuric nephrosis. Two other abnormalities have been observed during and after the hemolytic crisis. One is the occurrence of methemoglobinemia; the other is the presence of degenerative lesions in the white matter of the brain. There are a number of explanations for the development of hemolysis. One is that the erythrocytes in affected sheep become immunogenic as a result of the copper accentuation. It is suggested that this immunogenicity leads to the development of an autoantibody and the final result of an autoimmune hemolytic anemia [5].
Alternatively, copper may act as an oxidant on the red cell membrane, leading to membrane damage and acute hemolysis as a result of oxidant injury. This is consistent with the formation of methemoglobin, a result of oxidant effects during the acute hemolytic crisis. The liberation of the hepatic copper is incompletely understood, but the favored hypothesis is that the accumulation of copper ions in the liver cells is associated with the accumulation of electron-dense Iysozymes in the hepatocytes and their eventual necrosis. Various stresses including a fall in plane of nutrition, traveling, and lactation, are considered to precipitate the liberation. Complex mechanisms relating to disorders of cell membranes, a marked change in hemoglobin composition, including the development of methemoglobinemia and an increase in the oxidative status, are described as occurring during the critical stages. During the prehemolytic stage of several weeks before the crisis there is hepatic necrosis and an elevation of levels of liver-specific enzymes. A much more serious necrosis of liver occurs at the time of the hemolytic crisis [5].
Exposure to environmental contaminants has been suggested to play a role in the pathophysiology of adverse reproductive health effects including decreased semen quality, subfertility, change in birth sex ratio, and an increase in the prevalence of developmental abnormalities of the male reproductive tract [6, 7]. The aim of the current study was to evaluate beneficial effects of vitamin C on testes following long-term administration of copper sulfate in mice.

Material and method:
Thirty-six sexually mature male NMRI mice were purchased from The Animal Laboratory of Kerman University of Medical Sciences (KUMS), Kerman, Iran and kept in the Center for Laboratory Animal Care at the Veterinary Medicine Faculty of Shahid Bahonar University of Kerman for 1 week before treatment. The mice weighed 25�30 g and were of the same age (1.5�2 months old). The experimental animals were randomly divided into three  groups of 12 animals and were housed in standard polypropylene cages with wire mesh top, at 21 �C in a 12/12-h dark/light cycle. During the study, the animals received water and pellet food (Javaneh Khorasan Co, Mashhad, Iran) ad libitum. All ethical considerations using animals were considered carefully and the experimental protocol was approved by the Ethics Committee of KUMS.
 Experimental design
The study comprised three different groups of 12 mice as follows: the first group (group Cu) which is treated by gavage with copper sulfate at a dose of 200 mgkg"1day"1 (0.2 ml) and 0.1 ml of distilled water daily via IP injection for 6 weeks, the treatment group (group Cu + Vit C) which is treated by gavage with copper sulfate at a dose of 200 mgkg"1day"1 (0.2 ml) and received 10 mgkg"1day"1 (0.1 ml) vitamin C by IP injection, and the control group (group C) which received the same volume of distilled water by gavage and IP injection during experimental period.
Histopathological assays
After necropsy, the testes samples from six cases of 12 animals of each group were preserved in 10 % neutral buffered formalin solution for histological examination at fourth and sixth week. Formalin-fixed samples were processed by the standard paraffin wax technique, and sections of 5 �m thickness were cut and stained with hematoxylin and eosin.
Morphometrical assays
For morphometric assays, the seminiferous tubule diameter was measured in each testis. The ten smallest, roundest tubules were selected for each animal per group, and the diameter of tubules measured with an ocular micrometer under light microscopy. The number of round spermatids for each pachytene primary spermatocytes (meiotic index) was also calculated for determination of cell loss percentage during cell division [8]. Spermatogenesis was determined by the semi-quantitative testicular biopsy score count (Johnsen score, Table 1) in 100 cross-sections in each case at the same magnification and was summed up as mean Johnsen score (MJS) [9].

Table 1: Testicular biopsy score count (Johnsen score)

Score 	Histologic findings

10	Complete spermatogenesis, numerous spermatozoa, germinal epithelium of regular height, tubular lumen of normal diameter
9 	Numerous spermatozoa, germinal epithelium disorganized with sequestration of germinal cells, tubular lumen obturated
8 	Less than 5�10 spermatozoa per tubular cross-section
7 	No spermatozoa, numerous spermatids, spermatozytes and spermatogonia
6 	No spermatozoa, 5�20 spermatids, numerous spermatozytes and spermatogonia per cross-section
5 	No spermatozoa and spermatids, numerous spermatocytes and spermatogonia
4 	No spermatozoa and spermatids, less than five spermatozytes, but numerous spermatogonia per cross-section
3 	Only spermatogonia
2 	No germinal cells, only Sertoli cells (Sertoli-cell-only syndrome)
1	 No cells at all within the tubules



Statistical analysis
All data were expressed as mean � standard error of the mean. Statistical analysis was performed using one-way analysis of variance, followed by post hoc Tukey HSD test for seminiferous tubule diameter and meiotic index and mann-whitney (Non parametric) for Johnsen score evaluation. A value of P<0.05 was considered statistically significant.

Results:
Figures 1 and 2 illustrate sections from testes of animals in copper and treatment group, respectively. Histopathological lesions of testes of Cu group were included: shrinkage and collapse of tubules, decreased number of germinal cells and decrease in epithelial height. Also, the number of seminiferous tubules containing spermatozoa was decreased (Fig 1). The seminiferous tubules of treatment group show normal morphology with presence of spermatozoa in their lumen (Fig 2).
Tables 1, 2 and 3 show the number of round spermatids for each pachytene primary spermatocytes (meiotic index), the seminiferous tubule diameter and the semi-quantitative testicular biopsy score count (Johnsen score) in each case, respectively.

Discussion:
The role of copper in male reproductive capacity appears to be largely unknown, but this heavy metal appears to be involved in sperm motility and it may also act at the pituitary receptors, which control the release of LH [10].
It is known that copper is an essential trace element that plays an important role in several enzymes such as superoxide dismutase. Human spermatozoa are particularly susceptible to peroxidative damage because they contain high concentrations of polyunsaturated fatty acids and also possess a significant ability to generate reactive oxygen species (ROS), mainly superoxide anion and hydrogen peroxide. Superoxide dismutase protects human spermatozoa from this peroxidative damage. Oxidative stress caused by accumulated ROS is closely involved in a variety of pathological processes. Germ cells are as vulnerable as other cells to the potential detrimental effects of ROS and may thus require antioxidant protection at sites of gamete production, maturation and storage and embryo implantation [11]. It is reported that copper acts as a catalyst in the formation of ROS which can lead to oxidative stress and destructive lipid peroxidative damage [12]. Copper might be mediator of the effect of oxidative damage and play an essential role in spermatogenesis and male infertility [13].
It has been shown that copper in vitro increased lipoprotein oxidation [14, 15]. Spermatozoa are highly susceptible to damage by excess concentrations of ROS due to the high content of polyunsaturated fatty acids within their plasma membrane and, although conventional basic semen characteristics other than motility are not obviously influenced by the oxidative state of semen [16], such damage may underlie several aspects of male infertility. Increased lipid peroxidation and altered membrane function can render sperm dysfunctional through impaired metabolism, motility, acrosome reaction reactivity and fusogenic capacity as well as oxidative damage to sperm DNA [17].
Results of previous studies showed the beneficial effects of vitamin C on epididymal sperm quality following experimentally induced copper poisoning in mice [18]. This study demonstrates that the spermatogenic damage due to long-term administration of copper can be improved by vitamin C therapy. In our experiment, the spermatogenic process reduced after copper poisoning because of damage to the germ cells, the pachytene spermatocytes and early spermatids. As the length of time from initiation of stem cell division to formation of spermatozoa is around 35 days for mice [19], the chosen period of time (6 weeks) provided sufficient time to monitor the potential recovery of spermatogenesis in surviving spermatogonia. Previous investigations have proved that copper overload can cause cellular damage by different mechanisms.
The pathological manifestations observed during this study are indicative of copper toxicosis [20]. Similar results have been described in naturally occurring cases in young animals [21]. The data obtained show that copper sulphate at a dose of 200 mg kg-1 day-1 after 6 weeks that caused frank testicular atrophy correspondingly reduced sperm density in epididymal lumen, lowered motility and induced structural abnormalities in spermatozoa. The deterioration of seminiferous germinal epithelium or a spermicidal effect of copper sulphate may be responsible for such effects.
Vitamin C is one of several antioxidative vitamins, which have been postulated to minimize testicular cytotoxic effects in animals treated with pesticides, chemical mutagens, xenobiotics, and metals [22, 23]. The exact mechanism of the protective action of vitamin C against ROS-induced toxicity is not in detail understood. However, it is believed that vitamin C, as an antioxidant, might prevent the production of mutagenic electrophilic metabolites [24] and stimulate 7-a-hydroxylation of lipids and cholesterol nuclei, thus enhancing their degradation to bile acids, which could be excreted from the body. Alternatively, vitamin C, as a part of a redox buffer system, can effectively scavenge harmful ROS [25]. Such antioxidative action of vitamin C could relieve the male germ cells from oxidative damage, thereby increasing sperm count and decreasing the percentage of abnormal sperm population.

Conclusions:
Considering nontoxic and safe nature of vitamin C, it can be one of the suitable choices for preventive therapeutic effects and/or improvement in testicular tissue after Cu toxicosis. More research work is needed to reveal the exact mechanism of vitamin C on the hormonal regulation of the testis and epididymis.

Acknowledgments: 
 This research was financially supported by a grant for scientific research from the research council of Shahid Bahonar University of Kerman, Iran.



References:
1. Goyer RA (1991) Toxic effects of metals. In: Amdur MO, Doull J, Klaasen CD (eds) Casarett and Doull�s toxicology, 4th edn. Pergamon, New York, pp 653�655
2. Stokinger HE (1981) Copper. In: Clayton GD, Clayton E (eds) Patty�s industrial hygiene and toxicology, vol 2A. Wiley, New York, pp 1620�1630
3. Rosmarie AF (1992) Toxicity summary for copper. Prepared for: Oak Ridge Reservation Environmental Restoration Program. Managed by Martin Marietta Energy Systems, Inc., for the US Department of Energy under contract no. DE-AC05-84OR21400
4. Venugopal B, Luckey TD (1978)Metal toxicity in mammals. 2. Chemical toxicity of metals and metalloids. Plenum, New York, pp 24�32
5. Radostits OM, Gay CC, Hinchcliff KW, Constable PD (2007) Veterinary medicine: a textbook of the disease of cattle sheep, pigs, goats and horses, 10th edn. Saunders, London, p 1822.
6. Carlsen E, Giwercman A, Keiding N, Skakkebaek NE (1992) Evidence for decreasing quality of semen during past 50 years. Br Med J 305:609�613
7. Swan SH, Elkin EP, Fenster L (2000) The question of declining sperm density revisited: an analysis of 101 studies published 1934�1996. Environ Health Perspect 108:961�966
8. Kheradmand A, Dezfoulian O, Tarrahi MJ (2010) Ghrelin attenuates heat-induced degenarative effects in the rat testis. Regul Pept 167:97�104.
9. Johnsen, SG (1970). Testicular biopsy score count - a method for registration of spermatogenesis in human testes: normal values and results in 335 hypogonadal males, Hormones 1(2), 25.
10. Slivkova J, Popelkova M, Massanyi P, Toporcerova S, Stawarz R, Formicki G et al (2009) Concentration of trace elements in human semen and relation to spermatozoa quality. J Environ Sci Health, Part A: Tox Hazard Subst Environ Eng 44:370�375.
11. Taylor CT (2001) Antioxidants and reactive oxygen species in human fertility. Environ Toxicol Pharmacol 10(4):189�198.
12. Stohs ST, Bagchi D (1995) Oxidative mechanisms in the toxicity of metals. Free Radic Biol Med 18:321�326
13. Aydemir B, Kiziler AR, Onaran I, Alici B, Ozkara H, Akyolcu MC (2006) Impact of Cu and Fe concentration on oxidative damage in male infertility. Biol Trace Elem Res 112:193�203
14. Abuja PM, Albertini R (2001) Methods for monitoring oxidative stress, lipid peroxidation and oxidant resistance of lipoproteins. Clin Chim Acta 306:1�17.
15. Raveh O, Pinchuk I, Fainaru M, Lichtenberg D (2001) Kinetics of lipid peroxidation in mixture of HDL and LDL, mutual effects. Free Radic Biol Med 31:1486�1497
16. Aitken RJ, Backer HWG, Irvine DS (1995) On the nature of semen quality and infertility. Hum Reprod 10:248�249
17. Cummins JM, Jequier AM, Kan R (1994) Molecular biology of human male infertility: links with aging, mitochondrial genetics and oxidative stress? Mol Reprod Dev 37:345
18. Sakhaee E, Abshenas J, Emadi L, Azari O, Kheirandish R, Samaneh A (2012). Effects of vitamin C on epididymal sperm quality following experimentally induced copper poisoning in mice. Comp. clin. P 1������������������I	J	N	m	�	�	�	����ʺ������������tdtStdtFthdo�6�CJ]�_H)aJ!hdo�hdo�6�CJH*]�_H)aJhdo�hdo�6�CJ]�_H)aJhdo�h�y�6�CJ]�_H)aJ!hdo�h�y�6�CJH*]�_H)aJhdo�hdo�6�]�_H)hdo�h�y�6�]�_H)hdo�h�y�6�H*]�_H)hdo�h�y�5�6�>*\�]�_H)
h�;"_H)h�;"h��5�CJ \�_H)aJ h�;"h�<�5�CJ \�_H)aJ h�;"h�[h5�CJ \�_H)aJ ������I	�	




')*no������������������$d�7$8$A$H$a$gd�$d�A$a$gdBwb$d�A$a$gda�$��d�7$8$A$H$`��a$gd�b $d�A$a$gdwh$d�A$a$gdwh�	�	�	�	



j
k
�
�
�
�
�
!"|}�����ſ������t�t�_M;M#h�B*CJOJQJ^JaJph#h�$B*CJOJQJ^JaJph)h�$h�$B*CJOJQJ^JaJph#h�b B*CJOJQJ^JaJph#ha�B*CJOJQJ^JaJph#hBwbB*CJOJQJ^JaJph)hBwbhBwbB*CJOJQJ^JaJph
h��_H)
h�;"_H)
h�y�_H)hp46�CJ]�_H)aJhdo�h�y�6�CJ]�_H)aJ!hdo�hdo�6�CJH*]�_H)aJ
|
�
�
�
�
�
�
�
�
�
���������&'*��������������׮��r�r�r`r�N#hBwbB*CJOJQJ^JaJph#h�B*CJOJQJ^JaJph)hh�8'B*CJOJQJ^JaJph#h�8'B*CJOJQJ^JaJph)h�8'h�8'B*CJOJQJ^JaJph'h�$B*CJOJQJ^J_H)aJph)h��h�$B*CJOJQJ^JaJph#h�$B*CJOJQJ^JaJph,h��h�$B*CJH*OJQJ^JaJph*34hmnp~���\_���������Ҩ��~l�Z�Z�Z�H3)h��h�5�B*CJOJQJ^JaJph#h()B*CJOJQJ^JaJph#hB�B*CJOJQJ^JaJph#h�/B*CJOJQJ^JaJph#h��B*CJOJQJ^JaJph#h�;"B*CJOJQJ^JaJph
h��_H)
hp	�_H)#h�B*CJOJQJ^JaJph#h�~�B*CJOJQJ^JaJph)h�h�B*CJOJQJ^JaJph/h�h�5�B*CJOJQJ\�^JaJphop~� �`av�!�!���������m$��d�7$8$A$H$`��a$gd��$��d�7$8$A$H$`��a$gd�b $d�A$a$gdwh$d�7$8$A$H$a$gdwh$��d�7$8$A$H$`��a$gd�{/$��d�7$8$A$H$`��a$gd�d$��d�7$8$A$H$`��a$gdwh$d�A$a$gdp	�
./Zx��������BCij�������'(LMst������$;<_`��������
/0W^xy����+,STyz������������������������������������������������������������������������������#h@�B*CJOJQJ^JaJph)h��h�5�B*CJOJQJ^JaJph)h��h()B*CJOJQJ^JaJphM��������KLpq������*+RS{�������!1BCjk������
34OPWp������@Aij������������������������������������ծծծծծծծծծծծծծծծծ�)h��h��B*CJOJQJ^JaJph#hB�B*CJOJQJ^JaJph)h��h�5�B*CJOJQJ^JaJph)h��h�Z�B*CJOJQJ^JaJphD��������"^_`auv����ɷ��~�~�~i`ZH6#h��B*CJOJQJ^JaJph#h�b B*CJOJQJ^JaJph
h��_H)h��h��_H))h��h��B*CJOJQJ^JaJph)h()h��B*CJOJQJ^JaJph#h�u�B*CJOJQJ^JaJph#h��B*CJOJQJ^JaJph#h�5�B*CJOJQJ^JaJph#h�dB*CJOJQJ^JaJph#h�]oB*CJOJQJ^JaJph#h@�B*CJOJQJ^JaJph���� ! �!�!�!�!�"�"�"�"�"�"�"($,$2$6$8$r$v$|$�$�$�%�%�%&�����خ؜؜؅؅�؅؅�؅؅��q�Y/hg61hg615�B*CJOJQJ\�^JaJph'h��B*CJOJQJ^J_H)aJph,h��h��B*CJH*OJQJ^JaJph#h�|B*CJOJQJ^JaJph/h�zXh��5�B*CJOJQJ\�^JaJph#h�b B*CJOJQJ^JaJph#h��B*CJOJQJ^JaJph)h��h��B*CJOJQJ^JaJph�!�%&|(�(�+�+,,2,4,�,'-_-�-.Q.����������������$7$8$A$H$gdp4$��d�7$8$A$H$`��a$gdp4$��d�7$8$A$H$`��a$gd�w�$��d�7$8$A$H$`��a$gd\xZ$��d�7$8$A$H$`��a$gdg61$��d�7$8$A$H$`��a$gd�|&((|(�()")T)V)�)�)�)�)**;*L*p*q*�*�*�*�*�*�*(+)+6+���������������������s^L^#h�;�B*CJOJQJ^JaJph)hp4hp4B*CJOJQJ^JaJph#h�c�B*CJOJQJ^JaJph#h��B*CJOJQJ^JaJph#h�D�B*CJOJQJ^JaJph)h\xZh\xZB*CJOJQJ^JaJph/h\xZh\xZ5�B*CJOJQJ\�^JaJph,hg61hg61B*CJOJQJ^JaJo(ph#hg61B*CJOJQJ^JaJph6+S+�+�+�+�+�+,,2,3,4,7,?/@/A/B/C/D/�������{�k�[G7��hp4CJOJQJ^J_H)aJ'j8h�w�CJOJQJU^J_H)aJh�w�CJOJQJ^J_H)aJh[UCJOJQJ^J_H)aJ'j�hp4CJOJQJU^J_H)aJ'jhp4CJOJQJU^J_H)aJhp4CJOJQJ^J_H)aJ$hp4hp4CJOJQJ^J_H)aJ#h��B*CJOJQJ^JaJph)hp4hp4B*CJOJQJ^JaJph#hp4B*CJOJQJ^JaJphQ.�.�./@/B/C/D/Y/�0�0�0�2�3�������������$��d�7$8$A$H$`��a$gd6�$��d�7$8$A$H$`��a$gd��$d�A$a$gdCa$d�7$8$A$H$a$gd�i$��d�7$8$A$H$`��a$gdg61$��d�7$8$A$H$`��a$gdp4$7$8$A$H$gdp4
D/Y/00"0'040F0W0s0�0�0�0�0�0�0#1%1��îîÜ�Շ�riWE0)h�h��B*CJOJQJ^JaJph#hE1.B*CJOJQJ^JaJph#h�)B*CJOJQJ^JaJphhCah��_H))hg61h$�B*CJOJQJ^JaJph)hg61hg61B*CJOJQJ^JaJph#hr[�B*CJOJQJ^JaJph)h\xZh#�B*CJOJQJ^JaJph#h#�B*CJOJQJ^JaJph#hg61B*CJOJQJ^JaJph/hg61hg615�B*CJOJQJ\�^JaJph%1E1F1S1�1�1�1�1�1�1�12!2"2=2M2d2�2�2�2�2�23
3*3.37383E3�3�3�3���������������ƴ��{�{�{�f�f�`WhCah��_H)
h:N/_H))hp4h6�B*CJOJQJ^JaJph)h\xZh6�B*CJOJQJ^JaJph#h6�B*CJOJQJ^JaJph#h:N/B*CJOJQJ^JaJph#hkY.B*CJOJQJ^JaJph#hE1.B*CJOJQJ^JaJph)h�h��B*CJOJQJ^JaJph#h��B*CJOJQJ^JaJph�3�3�3�4�8`;�>�@fD������u`$��d�7$8$A$H$`��a$gd�@$��d�7$8$A$H$`��a$gdXcD$��d�7$8$A$H$`��a$gd�r�$��d�7$8$A$H$`��a$gd�vn$��d�7$8$A$H$`��a$gd�F�$��d�7$8$A$H$`��a$gd�A$d�A$a$gdCa$��d�7$8$A$H$`��a$gd:N/�3�3�344D4E4y4z4~44�4�4�4�4�4&5'5^5_5�5�5�5�5�566676k6l6�6�6�6�677U7V7�7�7�7�7�7�7�7�7����������ر��������������������������������{#h�F�B*CJOJQJ^JaJph#h@DB*CJOJQJ^JaJph#hKwsB*CJOJQJ^JaJph)hKwshKwsB*CJOJQJ^JaJph#h��B*CJOJQJ^JaJph#h�AB*CJOJQJ^JaJph)h�Ah�AB*CJOJQJ^JaJph-�7,8-888I8J8�8�8�8�8�8�8�8�8�8
9>9?9v9w9�9�9�9�9::-:<:I:J:{:|:�:�:�:�:;;U;V;^;_;��������ش�؟�{�����������{������������i�#h�r�B*CJOJQJ^JaJph#h�i�B*CJOJQJ^JaJph#h�vnB*CJOJQJ^JaJph)h�vnh�vnB*CJOJQJ^JaJph#h�#�B*CJOJQJ^JaJph#h�RB*CJOJQJ^JaJph#h�F�B*CJOJQJ^JaJph)h�F�h�F�B*CJOJQJ^JaJph)_;`;�;<<8<9<i<j<v<<�<�<�<�<==A=B=�=�=�=�=�=�=�=�=>>;><>u>v>�>�>�>�>�>?���۴����������������ɴ������������{�i#h�DB*CJOJQJ^JaJph#hXcDB*CJOJQJ^JaJph)hXcDhXcDB*CJOJQJ^JaJph#hJ
"B*CJOJQJ^JaJph)hJ
"hJ
"B*CJOJQJ^JaJph#h�r�B*CJOJQJ^JaJph#h��B*CJOJQJ^JaJph#h�vnB*CJOJQJ^JaJph&???
?3?4?L?Y?Z?[?�?�?�?�?�?�?�?�?@@;@<@n@o@�@�@�@�@�A�A�B�B�C�CfD���ر؟رر؈؈ررررررv�vdvdv#h�@B*CJOJQJ^JaJph#h�[pB*CJOJQJ^JaJph,hXcDhXcDB*CJH*OJQJ^JaJph#h�DB*CJOJQJ^JaJph#hXcDB*CJOJQJ^JaJph)hXcDhA�B*CJOJQJ^JaJph)hXcDhXcDB*CJOJQJ^JaJph#hA�B*CJOJQJ^JaJph"fDgDtD�E�E�ETFUFVFWFcFG�G�HI�ILJ�J�KFL<M��������������������$��d�7$8$A$H$`��a$gd��$��d�7$8$A$H$`��a$gd$d�A$a$gdCa$��d�7$8$A$H$`��a$gdCafDgDrDsDtD�D�D�D�D�D�D0E1EjEtE�E�E�E�E�E�E�E�EFFFFFSFTFUFWFcFeF����ɷɷɷɷɷɷ���䍷ɷɍ{�{��r])h��h��B*CJOJQJ^JaJphhCah��_H)#h�[pB*CJOJQJ^JaJph)h�[ph�[pB*CJOJQJ^JaJph)hhCaB*CJOJQJ^JaJph#hB*CJOJQJ^JaJph)hhB*CJOJQJ^JaJph
hCa_H)hCah�[p_H)#hCaB*CJOJQJ^JaJph!eFfFGG�G�G�H�HII�I�I�K�K6Q7Q8Q9Q|Q�Q�Q���%�&�'�����������������Ʊ���va؟�)hu�hu�B*CJOJQJ^JaJph#hu�B*CJOJQJ^JaJphU)h��hu�B*CJOJQJ^JaJph#h�b�B*CJOJQJ^JaJph)h��h�b�B*CJOJQJ^JaJph#h�D[B*CJOJQJ^JaJph)h��h��B*CJOJQJ^JaJph#h��B*CJOJQJ^JaJph<M�M$N�NwOP�P7Q%���\�����$�������������������������$��d�7$8$A$H$`��a$gd�b�$��d�7$8$A$H$`��a$gdu�$��d�7$8$A$H$`��a$gd��athol. DOI 10.1007/s00580-012-1592-5
19. De Rooij DG, Russell LD (2000) All you wanted to know about spermatogonia but were afraid to ask. J Androl 21:776�798.
20. Stalker MJ, Hayes MA (2007) Liver and biliary system. In: Maxie MG (ed) Jubb, Kennedy, and Palmer�s pathology of domestic animals, 5th edn. Saunders Elsevier, Philadelphia, pp 297�388
21. Devoy J (2002) The diagnosis and pathology of an incident of copper poisoning in dairy replacement calves. Res Vet Sci 72(suppl 1):19
22. Alvarez JG, Touchstone JC, Blasco L, Storey BT (1987) Spontaneous lipid peroxidation and production of hydrogen peroxide and superoxide in human spermatozoa Superoxide dismutase as major enzyme protectant against oxygen toxicity. J Androl 8:348�388
23. Giralut L, Boudou A, Dufurc EJ (1998) 113Cd-3IP NMR and fluorescence polarization studies of cadmium(II) interactions with phospholipids in model membranes. Biochim Biophys Acta 1414:140�154
24. Dawson EB, Harris WA, Powell LC (1990) Relationship between ascorbic acid and male fertility. World Rev Nutr Diet 62:1�26
25. Salem MH, Kamel KI, Yousef MI, Hassan GA, EL-Nouty FD (2001) Protective role of ascorbic acid to enhance semen quality of rabbits treated with sublethal doses of aflatoxin B1. Toxicology 162:209�218




81�h:p^v���. ��A!��"��#��$��%�������(2*2�Dd��|#<�P
�
3�������3"����((���Dd��|#<�P
�
3�������3"����((���Dd��|#<�P
�
3�������3"����((��^2���� 0@P`p������2(�� 0@P`p������ 0@P`p������ 0@P`p������ 0@P`p������ 0@P`p������ 0@P`p��8X�V~_H)mH	nH	sH	tH	N`�NNormal$��A$CJ_HaJmH	sH	tH	DA �DDefault Paragraph FontRi�RTable Normal�4�
l4�a�(k �(No ListPK!����[Content_Types].xml���N�0E�H���-J��@%�ǎǢ|�ș$�ز�U��L�TB� l,�3��;�r��Ø��J��B+$�G]��7O٭V��<a���(7��I��R�{�pgL�=��r���8�5v&����uQ�뉑8��C����X=��$␴�?6N�JC������F�B.ʹ'�.�+���Y�T���^e5�5�� ��ð�_�g -�;�����Yl�ݎ��|6^�N��`�?���[��PK!�֧�6_rels/.rels���j�0���}Q��%v/��C/�}�(h"���O�
����=������ ����C?�h�v=��Ʌ��%[xp��{۵_�Pѣ<�1�H�0���O�R�Bd���JE�4b$��q_����6L�R�7`������0̞O��,�En7�Li�b��/�S���e��е�����PK!ky���theme/theme/themeManager.xml�M
� @�}�w��7c�(Eb�ˮ��C�AǠҟ����7��՛K
Y,�
�e�.���|,���H�,l����xɴ��I�sQ}#Ր���� ֵ+�!�,�^�$j=�GW��)�E�+&
8���PK!0�C)��theme/theme/theme1.xml�YOo�6��w toc'vu�ر�-M�n�i���P�@�I}��úa��m�a[�إ�4�:lЯ�GR��X^�6؊�>$�������!)O�^�r�C$�y@�����/�yH*��񄴽)�޵��߻��UDb�`}"�qۋ�Jח���X^�)I`n�E���p)���li�V[]�1M<������O�P��6r�=���z�gb�Ig��u��S�eb��O������R�D۫����qu	�g��Z����o~ٺlAp�lx�pT0���+[}`j���zA��V�2�F���i�@�q�v�֬5\|��ʜ̭N��le�X�ds���jcs���7���f����
��W��+�Ն�7����`���g�Ș��J���j|��h(�K��D-����
dX��iJ�؇(��x$(��:��;�˹!�I_�T��S1�����?E��?�����?ZBΪm���U/������?�~����xY���'���y5�g&΋/����ɋ�>���G�M�Ge���D�����3Vq%'#q�����$�8��K�����)f�w9:ĵ��
x}r�x����w���r�:\TZaG�*�y8I�j�bR��c|XŻ�ǿ�I
u3KG�nD1�NIB�s���
��R��u���K>V�.EL+M2�#'�f��i~�V��vl�{u8��z��H�
�*���:�(W�☕
~��J�T�e\O*�tHG��HY��}KN�P�*ݾ˦���TѼ�9/#��A7�qZ��$*c?���qU��n��w�N��%��O��i�4=3��N���)cbJ
u�V�4����(Tn���
7��_?���m-ٛ�{U���B�w�<w���_���$�#��[Ի�8{���(�/�$Ϫ0h݋�F۴��®{L�)#7�i�%�=A�:s�$�),��Qg20pp��f
\}DU4�p
M{��DB��%J������+{�l�C���]��=��5
2F��hsF+��Y��\Ɉ�n�ì��:3���E�[��6�9����`��&45Z!��*��5k8�`Fmw��-��"�d>�z��n���ʜ"Z��x��J�Z��p;�������{/�<�P;��,)''K�Q�k5���q��pN��8�K�Gb�e���
�S��d�̛�\17	�p�a�>��SR!���

3��K4'+�r�zQ
TT��I����Ivt]K�c⫲�K#�v�5+�|��D������~��O@%\w���_�nN[�L��9K���q��g�V�h��n
R!�y+��U�n�;�*&�/H�r��T�	�>��>\
�t��=.Tġ
���S; Z�~�!����P��9gi���C�ڧ!�#	B��,��;�X=ۻ,I�2UW�V�9$l�k���=A��j���;�{�A�P79�|s*Y�����;�̠�[�MC�ۿ�hf��]o��{oY=1k�yV��V���5E8�Vk+֜���\8���0X4D)�!!��?*|f�v�
u���"�x��A�@T_������q��6�4)kڬu�V�7��t�'��%;���i�9s�9�x���,��ڎ-45x�d���8?�ǘ�d�/Y|t��&LIL�J`�& �-G�t�/��PK!
ѐ��'theme/theme/_rels/themeManager.xml.rels��M
�0���wooӺ�&݈Э���5
6?$Q��
�,.�a��i����c2�1h�:�q��m��@RN��;d�`��o7�g�K(M&$R(.1�r'J��ЊT���8��V�"��AȻ�H�u}��|�$�b{��P����8�g/]�QAsم(����#��L�[������PK-!����[Content_Types].xmlPK-!�֧�60_rels/.relsPK-!ky���theme/theme/themeManager.xmlPK-!0�C)���theme/theme/theme1.xmlPK-!
ѐ��'�	theme/theme/_rels/themeManager.xml.relsPK]�
<?xml version="1.0" encoding="UTF-8" standalone="yes"?>
<a:clrMap xmlns:a="http://schemas.openxmlformats.org/drawingml/2006/main" bg1="lt1" tx1="dk1" bg2="lt2" tx2="dk2" accent1="accent1" accent2="accent2" accent3="accent3" accent4="accent4" accent5="accent5" accent6="accent6" hlink="hlink" folHlink="folHlink"/>�I
������	*���&6+D/%1�3�7_;?fDeF�)+,-/0124578:;<=?@o�!Q.�3fD<M�*.369>A�8�@�����������0�(	�
��B
�S����	?���	|�"}�"~�"�"��"��"��"��"��"�&4<<D�I�%0:BHH�IB*�urn:schemas-microsoft-com:office:smarttags�country-region�8*�urn:schemas-microsoft-com:office:smarttags�City�=		*�urn:schemas-microsoft-com:office:smarttags	�PlaceType�=*�urn:schemas-microsoft-com:office:smarttags	�PlaceName�9*�urn:schemas-microsoft-com:office:smarttags�place���$		����������%������������u����
^ky���5A����bijrJMo�������&�kr����. ; @ M { � � � � � )!6!E!R!m!z!�!�!�!�!�"�"�"�"#	#�#�#�%�%&&�'�'�()�*�*�-�-Q.[.�.�.G/T/�/�/�0�0�1�1%2-2�2�2Y3a3�3�364A4W6d6�7�7�8�8�8�8
99:9?9D9I9M9T9Y9\9^9f9k9r9�9�9�9�9�9�9�9�9�9�9::*:,:::B:*;3;7;=;�;�;�;�;�;�;E<H<g<n<r<{<<�<�<�<	==�=�=�=�=�=�=�=�=�=�=>> >$>4>;>�>�>�>�>�>?
???!?%?,?0?8?�?�?�?�?�?�?�?�?=@D@E@N@b@g@l@r@�@�@�@�@�@�@�@�@�@�@�@�@�@�@A
A`AdA�A�AB	B
BBBB"B'B+B2B6B=B�B�B�B�B!C'CCCJCOCRC�C�C�C�C�C�C�C�C�C�C�C�CDDDDD!DDDND�D�D�D�D�D�D
EE2E8E�E�E�E�E�E�E�E�E�E�EF
FxF{FF�F�F�F�F�FwG}G�G�G�G�G�G�G)H0H1H8H9H=H�H�H�H�H�H�H�H�H\IeIoIxI�I	��5<�8�8�9�9j:�:�:;F;L;==�B�B�D�D�D�D�D�D�E�EFF�G�G�I33333333333333337
7S8T8�8�8@;A;?>?>�C�C�C�C#D#D�D�D�D�D�I7
7S8T8�8�8@;A;?>?>�C�C�C�C#D#D�D�D�D�D�I�
� o�n��$()
T��~&LT�Rj��b J
"�;">4#5$�8'�)s+F.E1.kY.�/:N/�{/g61p4�B8�@�A�D@DXcDiI.5J�cM�S[U5	X�zX\xZ�D[�@_CaBwb�d�Mf�[hwh�iG;j�vn�]o�[pKws9
t,kvC,x�!y�|^v��b�A��v� e�B��D�u��;�p��<�p	��T��Z��D�r[��F��
���)P��r��.�@��u��~���������#�a�i��i��y���h�d
���do�"��c�id��#��w����Q�$��5�6��k��I�I�@��I�I�I�Ip��������D�Ih@hh@h"h$hL@h(hT@h@��Unknown������������G��* ��Times New Roman5��Symbol3.��* ��Arialc�AdvTT3713a231Times New Roman]�AdvP41153CTimes New RomanA���$B�Cambria Math"q���h/�Gw�^�
�>%��
�>%�����x���24sIsI3�����HX	�?�����������������������[h2!xx�����Histopathological evaluation of supportive effect of vitamin C on testes following long-term administration of copper sulfate in mice EhsanMRT Pack 25 DVDs����Oh��+'��0���(4DP\l	��
��
�������Histopathological evaluation of supportive effect of vitamin C on testes following long-term administration of copper sulfate in mice EhsanNormalMRT Pack 25 DVDs94Microsoft Office Word@e'@.1����@��8���
�>����՜.��+,��0php|�������
�O��%sI�Histopathological evaluation of supportive effect of vitamin C on testes following long-term administration of copper sulfate in mice Title	

 !"#$%&'()*+,-./0123456789:;<=>?@ABCDE����GHIJKLM����OPQRSTUVWXYZ[\]^_`abc����efghijk����mnopqrs��������vw��������z������������������������Root Entry��������	�F�-8��yData
������������F1Table��������N+*WordDocument
����:�SummaryInformation(������������dDocumentSummaryInformation8��������lMsoDataStore����������
8����8���3EG�TI�3�4VOGWVSZ0��Q==2����������
8����8��Item
����	�����Properties������������UCompObj����
r����������������	����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������<b:Sources SelectedStyle="\APA.XSL" StyleName="APA" xmlns:b="http://schemas.openxmlformats.org/officeDocument/2006/bibliography" xmlns="http://schemas.openxmlformats.org/officeDocument/2006/bibliography"></b:Sources><?xml version="1.0" encoding="UTF-8" standalone="no"?>
<ds:datastoreItem ds:itemID="{9D06D185-3B32-4776-9538-65954996B7E1}" xmlns:ds="http://schemas.openxmlformats.org/officeDocument/2006/customXml"><ds:schemaRefs><ds:schemaRef ds:uri="http://schemas.openxmlformats.org/officeDocument/2006/bibliography"/></ds:schemaRefs></ds:datastoreItem>��
����	�F Microsoft Word 97-2003 Document
MSWordDocWord.Document.8�9�q

Youez - 2016 - github.com/yon3zu
LinuXploit