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Biomedical subjects

D Cortes

Publications and source records attributed to D Cortes.

At least 55 records · Page 3Linked to original sources

Cherimolin-1, new selective inhibitor of the first energy-coupling site of the NADH: ubiquinone oxidoreductase (complex I).

The mechanism linking electron transport to proton translocation in the NADH:ubiquinone oxidoreductase (complex I of the mitochondrial respiratory chain) is still unclear. Inhibitors acting at different sites of the enzyme are powerful tools to clarify this mechanism. Up to now, a unique inhibitor, the Annonaceous acetogenin rolliniastatin-2, selectively blocks the most internal proton-translocation site. This study introduces cherimolin-1, a new acetogenin that inhibits the complex I with this special mode of action, which is more easily available from the plant material. Moreover, the mode of action of this scarce type of complex I inhibitor is further characterized.

Animals↗

[Cryptorchidism in boys with anal atresia].

In a retrospective study of the case reports of 136 boys who were operated on for an imperforate anus and who survived at least 18 months, cryptorchidism was the most common associated anomaly, involving 26 cases (19%). The higher the level of the anorectal malformations, the higher was the incidence of cryptorchidism. The incidence of renal and ureteric malformations and dysplasias showed a parallel tendency. The incidence of vertebral malformations and dysplasias in the T10-S5 area was low among patients with a covered anus or a perineal fistula. Cryptorchidism was found to be associated with urological and with T10-S5 vertebral malformations and dysplasias. Recognition of this association is probably new. The histopathological findings of testicular biopsy specimens and the location of the undescended testes in patients with an imperforate anus showed the same pattern as seen in undescended testes from patients with cryptorchidism only. These findings, together with the existing literature on the subject, indicate that further studies on the association of cryptorchidism, urological, and T10-S5 vertebral malformations and dysplasias may be important for a better understanding of cryptorchidism in general.

Abnormalities, Multiple↗

[Laparoscopy in 100 consecutive patients with 128 impalpable testes].

A cohort of 100 patients underwent laparoscopy for 128 impalpable testes. They ranged in age from 2.7 to 19.3 years (median 10.8 years). There were no complications associated with laparoscopy. In 50% of the cases either blindending cord structures above the internal inguinal ring or intra-abdominal testes were identified; in the remainder, cord structures could be seen passing through the ring, indicating an intracanalicular testis. The impalpable testis was absent in 77% of patients with a contralateral scrotal testis. A seminoma was found in one 18.6-year-old patient with bilateral cryptorchidism. No intratubular germ cell neoplasia (carcinoma in situ) was proved. Germ cell hypoplasia or aplasia was demonstrated in 95% of cases with testicular parenchyma. We recommend laparoscopy as a safe procedure which leads to a diagnosis in patients with impalpable testes; the advent of laparoscopic procedure makes definitive treatment possible in about 50% of such cases.

Adolescent↗

Acetogenins from Annonaceae, inhibitors of mitochondrial complex I.

One-hundred and twenty-eight different linear, epoxy, mono-tetrahydrofuran, bis-tetrahydrofuran or tri-tetrahydrofuran acetogenins have been isolated from the Annonaceae. These new secondary metabolites are potent cytotoxic inhibitors of the mitochondrial NADH:ubiquinone oxidoreductase (complex I of the respiratory chain).

Enzyme Inhibitors↗

Annosenegalin and annogalene: two cytotoxic mono-tetrahydrofuran acetogenins from Annona senegalensis and Annona cherimolia.

Two new cytotoxic mono-tetrahydrofuran acetongenins, annosenegalin and annogalene, have been isolated from the cytotoxic methanolic extract of Annona senegalensis and A. cherimolia seeds. Their structures were established on the basis of 1D and 2D NMR spectroscopic techniques. Annosenegalin belongs to the rare type of C37 mono-tetrahydrofuran acetogenins, and annogalene is an olefinic acetogenin.

Animals↗

Fertility potential after unilateral orchiopexy: an age independent risk of subsequent infertility when biopsies at surgery lack germ cells.

PURPOSE: We evaluated whether adult fertility potential was better when unilateral orchiopexy was done at ages 2 to 6 years or later, and we identified those at risk for infertility. MATERIALS AND METHODS: Unilateral orchiopexy was performed simultaneously with testicular biopsy in 11 patients 2.8 to 6.8 years old and in 54, 10.0 to 11.9 years old. In adulthood measurement of testicular volume, serum follicle-stimulating hormone, luteinizing hormone and testosterone was done, as well as analysis of semen specimens. RESULTS: At orchiopexy the 2 groups were statistically similar, and statistically similar fertility potentials were found in adulthood. Five of the 65 patients (7.7%, 95% confidence limits 2.5 to 17%) may experience infertility, representing 33% of both groups with less than 1% of the age matched number of spermatogonia per tubular transverse section (approximately no germ cells) in the biopsy specimen at orchiopexy. CONCLUSIONS: Between ages 2 and 12 years the timing of unilateral orchiopexy may vary without an effect on subsequent fertility potential. When biopsy at surgery lacks germ cells, there is an approximately 33% age independent risk of subsequent infertility. Otherwise patients may be fertile after unilateral orchiopexy between ages 2 and 12 years.

Age Factors↗

Fertility potential after unilateral orchiopexy: simultaneous testicular biopsy and orchiopexy in a cohort of 87 patients.

PURPOSE: We investigated the prognostic value of the number of spermatogonia per tubular cross section in a testicular biopsy specimen obtained at orchiopexy for unilateral cryptorchidism. MATERIALS AND METHODS: A total of 87 consecutive 10 to 12-year-old cryptorchid boys underwent testicular biopsy simultaneously with unilateral orchiopexy. In adulthood 56 of the 87 patients agreed to measurement of serum follicle-stimulating hormone, luteinizing hormone, testosterone and testicular volume, and 54 provided specimens for semen analysis. RESULTS: The number of spermatogonia per tubular cross section correlated to the volume of the operated testis and total testicular volume in adulthood. Serum follicle-stimulating hormone negatively correlated to these volumes, sperm concentration and total sperm count. Contralateral testicular volume correlated to sperm concentration, total sperm count, and percent of living and mobile sperm. When biopsy revealed Sertoli cells only or 1 spermatogonium per 100 tubular cross sections, the age matched number of spermatogonia per tubular cross section was 1% or less. Of these patients 33% later presented with 5 million spermatozoa per ml. or less, no normal motility and generally lower sperm concentrations that those with more than 1 spermatogonium per 100 tubular cross sections (greater than 1%) in the biopsy specimen. When the value was greater than 1%, later sperm quality was not significantly reduced in comparison to that of the general population. CONCLUSIONS: The age matched number of spermatogonia per tubular cross section is significant in regard to fertility potential, and a value of 1% or less (approximately Sertoli cells only) may predict low fertility potential. To our knowledge Sertoli cells only have not been observed before 15 months of life, which makes it logical to treat cryptorchidism before this age even in unilateral cases.

Biopsy↗

The pathogenesis of cryptorchidism and splenogonadal fusion: a new hypothesis.

OBJECTIVE: To obtain new information about the pathogenesis of cryptorchidism. MATERIALS AND METHODS: Published reports of 111 males with splenogonadal fusion were examined and the presence and type of cryptorchidism and the degree of continuity between the spleen and gonads determined. RESULTS: Of the 111 cases, 31% had cryptorchidism and of these 59% were bilaterally cryptorchid; 26% and 65% had right and left intra-abdominal testes, respectively. Of those with continuous splenogonadal fusion, 44% had cryptorchidism. Solely cryptorchid cases with splenogonadal fusion had reported bilateral absence of both legs, imperforate anus, spina bifida, diaphragmatic hernia and hypospadias. CONCLUSION: An hypothesis is proposed that the abnormal development of the diaphragmatic ligaments of the testes may lead to lack of their involution, with consequent cryptorchidism. In the case of splenogonadal fusion, the abnormal ligaments are colonized by splenic cells, possibly because of an abnormal proximity to the splenic anlage, with the resulting abnormal ligament persisting as the splenic cord and thus resulting in cryptorchidism. The basic abnormality may be in the connections of the diaphragmatic ligaments, caused by abnormal midline development in the third to fourth week of gestation.

Cryptorchidism↗

Cryptorchidism in boys with imperforate anus.

In a retrospective study of the case reports of 136 boys who were operated on for an imperforate anus and who survived at least 18 months, cryptorchidism was the most common associated anomaly, involving 26 cases (19%). The higher the level of the anorectal malformations, the higher was the incidence of cryptorchidism. The incidence of renal and ureteric malformations and dysplasias showed a parallel tendency. The incidence of vertebral malformations and dysplasias in the T10-S5 area was low among patients with a covered anus or a perineal fistula. Cryptorchidism was found associated with urological and with T10-S5 vertebral malformations and dysplasias. Recognition of this association is probably new. The histopathological findings of testicular biopsy specimens and the location of the undescended testes in patients with an imperforate anus showed the same pattern as seen in undescended testes from patients with cryptorchidism only. These findings, together with the existing literature on the subject, indicate that further studies on the association of cryptorchidism, urological, and T10-S5 vertebral malformations and dysplasias may be very helpful toward a better understanding of cryptorchidism in general.

Abnormalities, Multiple↗

Effects of various isoquinoline alkaloids on in vitro 3H-dopamine uptake by rat striatal synaptosomes.

Various alkaloids having an isoquinoline skeleton from different species of the Annonaceae, Fumariacae, and Aristolochiacae (aporphine, cularine, benzylisoquinoline, and bisbenzylisoquinoline derivatives) were tested for their ability to inhibit in vitro 3H-dopamine uptake by rat striatal dopamine D1 3H-SCH 23390 AND D2 3H-raclopride binding sites. Except for some aporphine derivatives (anonaine [1], norstephalagine [2], isopiline [3]) and some bisbenzylisoquinoline alkaloids (dimethylgrisabine [27], antioquine [28], obaberine [29], isotetrandrine [30]) that displayed affinities of the same order as the reference compounds (nomifensine [38], amineptine [39], dexamphetamine [40]), the other tested products had low, or no, affinity on the 3H-dopamine uptake since, in comparison, its affinity at dopamine D1 3H-SCH 23390 and D2 3H-raclopride binding sites was low. These data suggest that it could be possible to synthesize anonaine-like products displaying intense dopamine-uptake inhibitory properties, which could lead to a potential antidepressant activity.

Alkaloids↗

Laparoscopy in 100 consecutive patients with 128 impalpable testes.

OBJECTIVE: To investigate the value of laparoscopy in boys with impalpable testes, to carry out a histological examination of testicular biopsies or orchidectomy specimens, and to present a clinical description of boys with impalpable testes. PATIENTS AND METHODS: One hundred consecutive patients underwent laparoscopy for 128 impalpable testes. They ranged in age from 2.7 to 19.3 years (median 10.8). Histological examination was performed on 39 testicular biopsies, nine primarily orchidectomized testes and 13 tissue samples from the end of blind-ending vessels and vasa deferentia. Any additional diagnoses to that of impalpable testes were recorded. RESULTS: There were no complications associated with laparoscopy and the procedure clarified the situation in all patients. In 50% of patients either blind-ending cord structures above the internal inguinal ring or intra-abdominal testes were identified; in the remainder, cord structures could be seen passing through the ring, indicating an intracanalicular testis. The impalpable testis was absent in 77% of patients with a contralateral scrotal testis. A seminoma was found in one 18.6-year-old patient with bilateral cryptorchidism. No intratubular germ cell neoplasia (carcinoma in situ) was found. Germ cell hypoplasia or aplasia was demonstrated in 95% of patients with testicular parenchyma. Additional diagnoses were made in 49% of patients with bilaterally undescended testes (one or both of which were impalpable). CONCLUSION: We recommend laparoscopy as a safe procedure which leads to a diagnosis in patients with impalpable testes; the advent of laparoscopic procedures makes definitive treatment possible in about 50% of such patients. Open procedures will be indicated only to ascertain the quality and treatment of intracanalicular testes.

Adolescent↗

Vasodilator effects of liriodenine and norushinsunine, two aporphine alkaloids isolated from Annona cherimolia, in rat aorta.

The effect of two aporphines, liriodenine and norushinsunine, isolated from Annona cherimolia, were studied in the rat aorta in order to examine their mechanism of action. Both alkaloids (10(-7) - 10(-4) mol/l) showed relaxant effects on the contractions elicited by 10(-6) mol/l noradrenaline (NA) or 80 mmol/1 KCl, but, while liriodenine showed a nonspecific relaxant action on both spasmogens, norushinsunine was more potent on KCl-induced contraction. In Ca2+ free medium, both alkaloids (0.1 mmol/l) inhibited the responses elicited by NA, but not those elicited by caffeine. This inhibitory action occurred when the alkaloids were present during the release of the Ca2+ internal stores or during the refilling process. These results suggest that the two aporphines show a relaxant action in rat aorta which is mediated by an interaction with alpha1-adrenoceptors and an alteration of the Ca2+ entry via voltage-operated channels. Norushinsunine exhibits a certain degree of selectivity as an L-type Ca2+ channel blocker.

Alkaloids↗

Quantitative histology of germ cells in the undescended testes of human fetuses, neonates and infants.

PURPOSE: We investigated the number of germ cells per tubular cross section and testicular weight in cryptorchid fetuses, neonates and infants, and characterized additional abnormalities. MATERIALS AND METHODS: Our series comprised 35 fetuses and 58 boys with cryptorchidism, and 22 normal fetuses and 25 normal boys. Age ranged from 28 weeks of gestation to 3 years. RESULTS: Cryptorchid fetuses had reduced germ cells per tubular cross section values and lower testicular weights. Values were reduced in cryptorchid boys without a symptomatic inguinal hernia. If a hernia was present, values were normal in the first year of life but decreased at age 1 to 3 years. Malformations or dysplasia of the kidneys, ureter or T10 to S5 vertebrae were present in 34% of the cryptorchid fetuses and 18% of the cryptorchid boys without a symptomatic inguinal hernia. CONCLUSIONS: Our study suggests a reduced number of germ cells in undescended testes from week 28 of gestation and germ cell hypoplasia as a consequence of continued postnatal undescended testicular position. Cryptorchidism may result from abnormal development of the caudal developmental field.

Abnormalities, Multiple↗

Natural substances (acetogenins) from the family Annonaceae are powerful inhibitors of mitochondrial NADH dehydrogenase (Complex I).

Natural products from the plants of the family Annonaceae, collectively called Annonaceous acetogenins, are very potent inhibitors of the NADH-ubiquinone reductase (Complex I) activity of mammalian mitochondria. The properties of five of such acetogenins are compared with those of rotenone and piericidin, classical potent inhibitors of Complex I. Rolliniastatin-1 and rolliniastatin-2 are more powerful than piericidin in terms of both their inhibitory constant and the protein-dependence of their titre in bovine submitochondrial particles. These acetogenins could be considered therefore the most potent inhibitors of mammalian Complex I. Squamocin and otivarin also have an inhibitory constant lower than that of piericidin, but display a larger protein-dependence of the titre. Squamocin and otivarin, contrary to the other acetogenins, behave qualitatively like rotenone. Rolliniastatin-2 shows unique properties as its interaction, although mutually exclusive to that of piericidin, appears to be mutually non-exclusive to that of rotenone. It is the first time that a potent inhibitor of Complex I is found not to overlap the active site of rotenone.

Animals↗

Examination for intratubular germ cell neoplasia at operation for undescended testis in boys.

A total of 843 consecutive boys (median age 12.7 years) who had undergone testicular biopsy at operation for undescended testis was followed into adulthood (median age 25.2 years) to examine for testicular germ cell neoplasia. Five cases of testicular germ cell neoplasia were identified, including 1 nonseminoma of the contralateral testis, which had been treated before surgery for an undescended testis, 1 nonseminoma found at followup, 1 seminoma and 2 intratubular germ cell neoplasms. Of the later 3 patients 1 had a 45,X/46,XY karyotype and 2 had abnormal external genitalia. Previous testicular biopsy from the patient in whom nonseminoma was noted at followup showed Sertoli cells only. We recommend that testicular biopsy be performed at operation for undescended testis in boys with abnormal sex chromosomes, particularly 45,X/46,XY karyotype, and in those with abnormal external genitalia. The pattern of Sertoli cells only in biopsies from boys does not preclude the occurrence of testicular cancer in adulthood.

Biopsy↗