In order to facilitate the simultaneous search of structural and pharmacological information for drugs, we studied the design of the coding system for pharmacological information.  In this study, pharmacological information was defined as information that describes the nature of principal action, specifically “where and how the drug acts”.  Furthermore, we developed a standardized code generation system for describing such information.  First, in order to describe the drug delivery location, organs and subcellular organelles were assigned hierarchical codes by referring to the hierarchical classification of human anatomy.  Next, drug interacting receptors and their action results were encoded and coupled to the location codes, and procedures for generating pharmacological information codes were developed.  Regarding drug structure information, Cartesian coordinates that describe the planer structure were transformed into sequences of numbers in order to obtain molecular fingerprints, which were then used to generate drug structural information codes.  Drug information was compiled into a database that comprises the two categories of codes (pharmacological/structural codes), and a simultaneous search system was developed that links structural similarity and pharmacological information.  A web-based interface for searching the structural information codes was created, and searches could be performed as expected.

AIMTo investigate the effects of rat Erythropoietin (Epo) on spermatogenesis by transferring rat Epo gene into cryptorchid testes by means of in vivo electroporation.

METHODSSprague-Dawley rats with surgically-induced unilateral cryptorchidism were divided into three groups: the first group was given intratesticular injections of pCAGGS-Epo (pCAGGS-Epo group), the second group was given intratesticular injections of pCAGGS (pCAGGS group), and the third group were given intratesticular injections of phosphate-buffered saline (PBS group). At the same time, square electric pulses of 30 V were applied six times with a time constant of 100 ms. One or two weeks after injection, each testis was weighed and the ratio of the total number of germ cells to that of Sertoli cells (G/S ratio) was calculated to evaluate the impairment of spermatogenesis. Ten testes taken from each of the three groups were examined at each time point.

RESULTSThe testicular weight after the injection of pCAGGS-Epo or pCAGGS control plasmid was (0.85+/-0.08) g and (0.83+/-0.03) g, respectively, at week 1 (P = 0.788) and (0.62+/-0.06) g and (0.52+/-0.02) g, respectively, at week 2 (P = 0.047). At week 1, spermatids and sperm were more abundant in testes with pCAGGS-Epo than those in the control testes. At week 2, spermatids and sperm were hardly detected in either group. The G/S ratio was 23.27 +/-6.80 vs. 18.63+/-5.30 at week 1 (P = 0.0078) and 7.16+/-3.06 vs. 6.05+/-1.58 at week 2 (P = 0.1471), respectively.

CONCLUSIONThe transfer of Epo to rat testes by in vivo electroporation may reduce the risk of the germ cell loss caused by cryptorchidism.

Animals ; Cryptorchidism ; pathology ; therapy ; Electroporation ; methods ; Erythropoietin ; genetics ; Genetic Therapy ; methods ; Lac Operon ; Male ; Organ Size ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Risk Factors ; Sertoli Cells ; cytology ; Spermatids ; pathology ; Spermatogenesis ; Spermatozoa ; pathology ; Testis ; pathology ; physiology

AIMSpermatogenic dysfunction may result from thickening of seminiferous tubular basement membrane (BM) with tubular sclerosis. Transforming growth factor beta1 (TGF-beta1) plays an important role in fibrogenesis. The intracellular and extracellular expression of TGF-beta1 in the testis were immunohistochemically determined, using LC antibody (LC) for intracellular TGF-beta1 and CC antibody (CC) for extracellular TGF-beta1.

METHODSTwenty-three testicular biopsy specimens were obtained from varicocele and five from Sertoli-cell-only (SCO) patients, and five from normal volunteers. The relative area involved by the expression of TGF-beta1 for CC or LC (TGF-beta1 index for CC or LC) was examined, and semen parameters and serum hormonal levels and TGF-beta1 were analyzed. The Johnson score (JS), the BM thickness, and the tubular diameter were also determined.

RESULTSImmunoreactivity for CC was hardly detected. That for LC was detected in the Sertoli and germ cells. The TGF-beta1 index for LC was significantly higher in the varicoceles than in the normal testes. Interestingly, that for LC was significantly higher in the varicoceles than in the SCO. The level of serum TGF-beta1 was significantly higher in varicoceles than in the normal testes.

CONCLUSIONThe distribution of the intracellular and extracellular expression of TGF-beta1 in human testis was demonstrated. It suggests that TGF-beta1 is related to fibrosis of seminiferous tubules and may lead to spermatogenic disruption.

Adult ; Biopsy ; Estrogens ; blood ; Follicle Stimulating Hormone ; blood ; Humans ; Luteinizing Hormone ; blood ; Male ; Prolactin ; blood ; Reference Values ; Sertoli Cells ; physiology ; Spermatogenesis ; physiology ; Testis ; cytology ; pathology ; physiology ; Testosterone ; blood ; Transforming Growth Factor beta ; blood ; metabolism ; Varicocele ; blood ; physiopathology