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Biomedical subjects

D Cortes

Publications and source records attributed to D Cortes.

At least 19 recordsLinked to original sources
PubMed2006

The relation of germ cells per tubule in testes, serum inhibin B and FSH in cryptorchid boys.

At bilateral orchiopexy bilateral biopsies may be indicated to determine fertility potential. It is currently unknown if the serum inhibin B levels at time of orchiopexy reflect the testicular status of the bilaterally cryptorchid child. The aim of this study was to relate the results of inhibin B and FSH measurements with testicular biopsy parameters in bilateral cryptorchid boys. Included were 25 boys with bilateral cryptorchidism, median 2.5 years (9 months to 5.5 years) at surgery for bilateral cryptorchidism with simultaneous testicular biopsies, and blood sample for inhibin B and FSH. The number of spermatogonia and gonocytes was measured in 100 tubular transverse sections, the S/T and the mean-S/T of the patient was found, and expressed as percent of lowest normal value. Inhibin B and FSH were measured and related to age-specific values. Forty percent (10/25) of the patients had very low mean-S/T (mean-S/T<10% of lowest normal-value). Inhibin B was decreased in 24% (6/25) of the patients, all with decreased mean-S/T, predominantly with a mean-S/T<10% of lowest normal-value (p<0.05). There was a negative correlation between inhibin B and FSH (p<0.05). In cases of mean-S/T<10% of lowest normal-value and decreased inhibin B, we found increased FSH in 9% (2/22) of the patients and hypergonadotropic hypogonadism was suspected. Low FSH was found in 5% (1/22) of the patients and hypogonadotropic hypogonadism was suspected. Low inhibin B predicts a serious condition in respect of infertility. Low FSH and inhibin B indicates examination for hypogonadotropic hypogonadism. In bilateral cryptorchid boys inhibin B levels correlated negatively to FSH.

Child, Preschool↗
PubMed2006

The incidence of bilateral cryptorchidism is increased and the fertility potential is reduced in sons born to mothers who have smoked during pregnancy.

PURPOSE: Recent studies have demonstrated a high prevalence of cryptorchidism, decreasing semen quality and increasing incidence of testicular cancer. These changes seem to be interrelated, and may be symptoms of a common underlying entity with foundations in fetal life. We investigated the influence of maternal smoking on fertility status in offspring cryptorchidism. MATERIALS AND METHODS: We prospectively studied consecutive patients presenting to the pediatric surgery department between 1996 and 2005. A total of 157 boys 1 to 5.9 years old underwent surgery for cryptorchidism with simultaneous testicular biopsy, and exhibited well preserved testicular parenchyma. Only white patients with Danish-speaking mothers who had reported pregnancy history including smoking habits during pregnancy and history of the offspring were included. The patients had cryptorchidism only and none received hormonal treatment before surgery. The number of spermatogonia and gonocytes per tubule cross-section was assessed and compared to normal values from autopsy material. RESULTS: The group of boys with cryptorchidism whose mothers had smoked heavily during pregnancy (ie more than 10 cigarettes daily throughout the pregnancy) had a significantly increased risk of bilateral cryptorchidism (52%, or 11 of 21 patients), and a decreased number of spermatogonia and gonocytes per tubule cross-section, which was absolute (0.097 [0 to 0.75]) and age related (14% [0% to 198%] of normal for age) compared to boys whose mothers did not smoke (20%, or 22 of 112 patients, 0.140 [0 to 2.14] and 37% [0% to 563%] of normal for age, p <0.01, p <0.05 and p <0.05, respectively). CONCLUSIONS: A close relationship between maternal smoking during pregnancy and adverse trends in offspring reproductive health in relation to cryptorchidism was observed.

Child, Preschool↗
PubMed2003

Infertility despite surgery for cryptorchidism in childhood can be classified by patients with normal or elevated follicle-stimulating hormone and identified at orchidopexy.

OBJECTIVE: To analyse infertility despite orchidopexy in childhood. PATIENTS AND METHODS: The study comprised patients with cryptorchidism (70 bilateral and 65 unilateral) who had a simultaneous biopsy taken at orchidopexy in childhood, and in adulthood had analyses of semen and FSH. In adulthood 42 formerly bilateral cryptorchid boys had repeat testicular biopsies taken. Infertility was suspected in men with < 5 million sperm/mL in the best sample of semen and concomitant poor sperm motility, and who were classified by follicle-stimulating hormone (FSH) values. At orchidopexy the number of spermatogonia/tubule and the germ cell differentiation were measured. In adulthood the percentage of tubules with complete spermatogenesis, spermatogenic arrest and Sertoli-cell only status was assessed. RESULTS: Infertility was suspected in 38 of 70 (54%) of formerly bilateral and six of 65 (9%) formerly unilateral cryptorchid patients. High FSH values were expected in these suspected infertile patients, but 15 of 38 (59%) formerly bilateral and five of six formerly unilateral cryptorchid patients had normal FSH values. These patients were identified in childhood at orchidopexy; those with bilateral cryptorchidism generally presented with germ cells, but the mean number of spermatogonia per tubule was < 30% of the lowest normal value, and the germ cells were seldom normally differentiated, whereas those with unilateral cryptorchidism generally lacked germ cells in the biopsies. No patients had a decreased FSH value. CONCLUSION: Despite surgery for cryptorchidism, infertility was probable in a third (44 of 135) of the patients. We expected high FSH values in these patients, but in 45% (20/44) the FSH values were normal. These patients may have relative FSH deficiency. At orchidopexy these patients were identified to be bilaterally cryptorchid with few germ cells and those unilaterally cryptorchid had none in the biopsy. After orchidopexy in childhood, additional hormonal treatment, e.g. recombinant FSH or buserelin, may be indicated in these patients.

Adolescent↗
PubMed2003

The results of 15 years of consistent strategy in treating antenatally suspected pelvi-ureteric junction obstruction.

OBJECTIVE: To determine how to select patients for surgery among those with antenatally detected pelvi-ureteric junction (PUJ) obstruction. PATIENTS AND METHODS: The study comprised 100 consecutive children with antenatally detected suspected unilateral PUJ obstruction and a normal contralateral kidney. The correct diagnosis was made using postnatal ultrasonography, intravenous urography and renal scintigraphy, the last also being used for the follow-up. RESULTS: Four patients had poor function in the hydronephrotic kidney, treated in three by nephrectomy; 61 had normal function in the hydronephrotic kidney, with 49 followed for 1-10 years with no change in kidney function and no symptoms. Twelve patients in this group had later surgery (at 0.7-8 years old) because of pyelonephritis (four), pain and/or renal functional impairment (eight, three of whom had normal function afterward). Thirty-five patients had moderately impaired function of the hydronephrotic kidney; 29 had primary surgery at a median age of 4 months. The median hydronephrotic renal function increased from 32% before to 42% after surgery, with 15 kidneys having normal function. In one other patient the kidney was lost before surgery. Five other patients were initially treated conservatively and the hydronephrotic renal function increased from 32% to 35% at the 1-year follow-up, significantly less than in the surgical group. The overall operative complication rate was 4%. CONCLUSIONS: With our management programme more than half the patients can avoid surgery in childhood. Although the follow-up was intense there was moderate and irreversible functional kidney deterioration in 5%. In contrast, after successful reconstructive surgery, only a few follow-up procedures causing possible discomfort to the child are needed in most. The risk of surgical complications cannot be neglected. The present results are useful for advising parents deciding whether their antenatally detected hydronephrotic child should undergo surgery or not.

Child↗
PubMed2001

Enantioselective syntheses of dopaminergic (R)- and (S)-benzyltetrahydroisoquinolines.

Optically pure (1S,R)- and (1R,S)-benzyltetrahydroisoquinolines (BTHIQs), 12a,b as the major diastereomers, were prepared by stereoselective reduction of the isoquinolinium salt possessing (R)- and (S)-phenylglycinol as the chiral auxiliary, respectively. The absolute configurations of (1S,R)-13a hydrochloride (O-debenzoylated derivative from 12a) and (1R,S)-12b diastereomers were unambiguously determined by single-crystal X-ray analysis. Reductive removal of the chiral auxiliary group, subsequent N-propylation, and cleavage of the methylenedioxy group furnished the optically active catecholamines (1S)-16a and (1R)-16b in good overall yield. We have separately prepared for the first time pairs of dopaminergic 1-BTHIQs enantiomers through a classical methodology in asymmetric synthesis. The (1S)-enantiomers (14a-16a) bind to D1 and D2 dopamine receptors with affinities 5-15 times higher than those of the corresponding (1R)-enantiomers (14b-16b). Moreover, (1S)-14a inhibits [3H]dopamine uptake with high affinity. It appears that synthesis and testing of (S)-enantiomers of BTHIQ are very important for the search for new active drugs at dopamine receptors.

Animals↗
PubMed2001

Gamma-lactone-Functionalized antitumoral acetogenins are the most potent inhibitors of mitochondrial complex I.

To study the relevance of the terminal alpha,beta-unsaturated gamma-methyl-gamma-lactone moiety of the antitumoral acetogenins of Annonaceae for potent mitochondrial complex I inhibition, we have prepared a series of semisynthetic acetogenins with modifications only in this part of the molecule, from the natural rolliniastatin-1 (1) and cherimolin-1 (2). Some of the hydroxylated derivatives (1b, 1d and 1e) in addition to two infrequent natural beta-hydroxy gamma-methyl gamma-lactone acetogenins, laherradurin (3) and itrabin (4), are more potent complex I inhibitors than any other known compounds.

Animals↗
PubMed2001

Cryptorchidism: aspects of fertility and neoplasms. A study including data of 1,335 consecutive boys who underwent testicular biopsy simultaneously with surgery for cryptorchidism.

PURPOSE: An attempt to make a rational strategy for treatment of cryptorchidism. MATERIALS AND METHODS: 1,335 cryptorchid boys with biopsy at surgery (1,638 specimens). We studied: frequency of no germ cells in biopsies from 698 patients <12 years at surgery; fertility potential of 140 patients who were now adults, and apperance of testicular neoplasia in all biopsies. RESULTS: Lack of germ cells appeared from 18 months. The frequency increased with increasing age. It appeared in 30% (61/202) bilateral, and 18% (88/496) unilateral cases. In men who had undergone bilateral or unilateral orchiopexy, respectively, there was normal sperm count in 19% (14/75) and 83% (54/65), and infertility was suspected in 56% (42/75) and 8% (5/65) (FE, p < 0.00005, p < 0.00005), respectively. The lowest, the mean, and the highest age-matched spermatogonia count per tubule at orchiopexy was associated with sperm count (Spearman test, p < 0.0001, p < 0.005, p < 0.05). Isolated, this was demonstrated for the 75 formerly bilateral (Spearman, p < 0.0001, p < 0.0001, p < 0.0001), but not the 65 formerly unilateral cases (Spearman, p = 1.0). No germ cells at orchiopexy was associated with suspected infertility. Risk was 78-100% in bilateral (dependent on one or both testes affected), and 33% in unilateral cryptorchidism. There was one invasive germ cell tumor, six cases of carcinoma in situ testis, and one Sertoli cell tumor. Three neoplasms were diagnosed in intra-abdominal testes, four in boys with abnormal external genitalia, and two in boys with known abnormal karyotype. Risk of neoplasia was 5% (7/150) in patients with intra-abdominal testis, abnormal external genitalia or diagnosed abnormal karyotype, versus 0% (0/1,185) in patients without these characteristics (FE, p < 0.00005). CONCLUSION: We recommend surgery for cryptorchidism before 15-18 months of age because: (a) lack of germ cells is very rare before, and (b) lack of germ cells is associated with subsequent risk of infertility. At primary surgery for cryptorchidism, we recommend examination for testicular neoplasia in cases of intra-abdominal testis, abnormal external genitalia or known abnormal karyotype.

Carcinoma in Situ↗
PubMed2001

Erythropoietin may reduce the risk of germ cell loss in boys with cryptorchidism.

PURPOSE: In boys with cryptorchidism older than 2 years a testicular biopsy at time of orchiopexy shows lack of germ cells in 10-40% of the cases. The number of spermatogonia per tubule is prognostic for subsequent fertility potential. A biopsy without germ cells is associated with 33-100% risk of infertility. In order to increase the number of germ cells, and thereby the fertility potential, additional hormonal therapy has been attempted before surgery. In a study, small doses of the gonadotropin-releasing hormone analogue buserelin before orchiopexy caused higher values. Others have found that hormonal treatment with human chorionic gonadotropin or gonadotropin releasing hormone analogue may harm the germ cells in cryptorchidism. The aim of the study is to demonstrate that additional hormonal therapy with erythropoietin has a positive effect on the number of germ cells. MATERIALS AND METHODS: Erythropoietin (Eprex) 100 IU/kg were administered subcutaneously weekly for 3 months prior to surgery in two cryptorchid boys, 6 months old and 1 year 9 months old, respectively, with renal function impairment. RESULTS: The number of spermatogonia per tubular cross-section in testicular biopsies was unusually high in both erythropoietin- treated cryptorchid cases compared to the control material of biopsies from the undescended testes of 698 cryptorchid patients and compared to the normal values. CONCLUSION: There are several hypothetic mechanisms that can explain the elevated number of spermatogonia seen in our erythropoietin treated cryptorchid patients. Erythropoietin may have a positive effect on germ cell proliferation in cryptorchidism.

Cryptorchidism↗
PubMed2001

Dieulafoy's disease of the bronchus in association with a paravertebral neurilemoma.

Dieulafoy's disease is a vascular anomaly characterized by the presence of a dysplastic artery that is related to an epithelial ulcer. While it is most frequently a GI condition, occurrence in the bronchus has been reported previously in six cases. We present the case of a 51-year-old man with severe hemoptysis and epistaxis. Chest radiographs showed diffuse density in the right base and a mass in the pedicle of T4. The results of bronchoscopy corroborated an active arterial bleeding point in the bronchus of the right middle lobe. A middle and lower lobectomy was performed with resection of the paravertebral mass. The final diagnoses were bronchial Dieulafoy's disease and paravertebral neurilemoma.

Arteriovenous Malformations↗
PubMed2000

Semisynthesis of antitumoral acetogenins: SAR of functionalized alkyl-chain bis-tetrahydrofuranic acetogenins, specific inhibitors of mitochondrial complex I.

The acetogenins of Annonaceae are known by their potent cytotoxic activity. In fact, they are promising candidates as a new future generation of antitumoral drugs to fight against the current chemiotherapic resistant tumors. The main target enzyme of these compounds is complex I (NADH:ubiquinone oxidoreductase) of the mitochondrial respiratory chain, a key enzymatic complex of energy metabolism. In an attempt to characterize the relevant structural factor of the acetogenins that determines the inhibitory potency against this enzyme, we have prepared a series of bis-tetrahydrofuranic acetogenins with different functional groups along the alkyl chain. They comprise several oxo, hydroxylimino, mesylated, triazido, and acetylated derivatives from the head series compounds rolliniastatin-1, guanacone, and squamocin. Our results suggest a double binding point of acetogenins to the enzyme involving the alpha,alpha'-dihydroxylated tetrahydrofuranic system as well as the alkyl chain that links the terminal alpha, beta-unsaturated-gamma-methyl-gamma-lactone. The former mimics and competes with the ubiquinone substrate. The latter modulates the inhibitory potency following a complex outline in which multiple structural factors probably contribute to an appropriate conformation of the compound to penetrate inside complex I.

Animals↗
PubMed2000

Mechanism of vascular relaxation by thaligrisine: functional and binding assays.

In the present study we examine the mechanism by which thaligrisine, a bisbenzyltetrahydroisoquinoline alkaloid, inhibits the contractile response of vascular smooth muscle. The work includes functional studies on rat isolated aorta and tail artery precontracted with noradrenaline or KCl. In other experiments rat aorta was precontracted by caffeine in the presence or absence of extracellular Ca2+. In order to assess whether thaligrisine interacts directly with calcium channel binding sites or with alpha-adrenoceptors we examined the effect of the alkaloid on [3H]-(+)-cis diltiazem, [3H]-nitrendipine and [3H]-prazosin binding to cerebral cortical membranes. The functional studies showed that the alkaloid inhibited in a concentration-dependent manner the contractile response induced by depolarization in rat aorta (IC50 = 8.9+/-2.9 microM, n=5) and in tail artery (IC50 = 3.04+/-0.3 microM, n=6) or noradrenaline induced contraction in rat aorta (IC50 = 23.0+/-0.39 microM, n=9) and in tail artery (IC50 = 3.8+/-0.9 microM, n=7). In rat aorta, thaligrisine concentration-dependently inhibited noradrenaline-induced contraction in Ca2+-free solution (IC50 = 13.3 microM, n=18). The alkaloid also relaxed the spontaneous contractile response elicited by extracellular calcium after depletion of noradrenaline-sensitive intracellular stores (IC50 = 7.7 microM, n=4). The radioligand receptor-binding study showed that thaligrisine has higher affinity for [3H]-prazosin than for [3H]-(+)-cis-diltiazem binding sites, with Ki values of 0.048+/-0.007 microM and 1.5+/-1.1 microM respectively. [3H]-nitrendipine binding was not affected by thaligrisine. The present work provides evidence that thaligrisine shows higher affinity for [3H]-prazosin binding site than [3H]-(+)-cis-diltiazem binding sites, in contrast with tetrandrine and isotetrandrine that present similar affinity for both receptors. In functional studies thaligrisine, acted as an alpha1-adrenoceptor antagonist and as a Ca2+ channel blocker, relaxing noradrenaline or KCl-induced contractions in vascular smooth muscle. This compound specifically inhibits the refilling of internal Ca2+-stores sensitive to noradrenaline, by blocking Ca2+-entry through voltage-dependent Ca2+-channels.

Adrenergic alpha-Agonists↗
PubMed2000

Synthesis of N-diisopropyl phosphoryl benzyltetrahydroisoquinoline, a new class of mitochondrial complexes I and III inhibitors.

The synthesis of N-(O,O-diisopropylphosphoryl)-benzyltetrahydroisoquinoline (3) has been achieved in a 'one pot' procedure from imine (2) and diisopropyl-phosphorochloridate (1) generated in situ (POCl3 + iPrOH). Compound 3 is the first benzyltetrahydroisoquinoline derivative found to be a potent inhibitor of mitochondrial complexes I and III, and therefore it opens a new perspective with this series of compounds as they can be considered as new class of antitumor agents.

Animals↗
PubMed2000

3-acetylaltholactone and related styryl-lactones, mitochondrial respiratory chain inhibitors.

A novel furano-pyrone, 3-acetylaltholactone, and two other known styryl-lactones, altholactone and 5-acetoxyisogoniothalamin oxide, have been isolated from Goniothalamus arvensis (Annonaceae) stem bark. We report here the isolation and structural elucidation of these compounds with furane-pyrone and styryl-pyrone skeletons, postulating also for the first time their mechanism of cytotoxicity based on inhibition on mammalian mitochondrial respiratory chain.

Animals↗
PubMed2000

Preparation of dopaminergic N-alkyl-benzyltetrahydroisoquinolines using a 'one-pot' procedure in acid medium.

The preparation of N-methyl-BTHIQ (4) from N-phenylethyl-phenacetamide (1) by cyclization, reduction and N-alkylation in acid medium has been achieved in good yield in a 'one-pot' procedure. Acylation of imine (2) intermediate afforded the Z and E stereoselectivity in the enamide formation. 6-Hydroxy-BTHIQ (7) shows selectivity for D2 dopamine receptors, while its N-methylated homologue (8) displays higher affinities for both D1 and D2 receptor types, with an unexpected increase in D1 dopamine receptor affinity.

Dopamine Agents↗
PubMed2000

Insecticidal and mutagenic evaluation of two annonaceous acetogenins.

Annonaceous acetogenins represent a new class of bioactive compounds whose primary mode of action is the inhibition of NADH-ubiquinone oxidoreductase. Given the potential pesticidal use of such a class of compounds, we have further evaluated the antifeedant and insecticidal effects of squamocin and annonacin, two annonaceous acetogenins, on Spodoptera littoralis, Leptinotarsa decemlineata, and Myzus persicae. Additionally, to partially assess their environmental risk, we have also tested their mutagenicity in Salmonella typhimurium strains TA98, TA100, and TA102 in the presence and absence of a metabolic activation system. Among the test compounds, annonacin showed antifeedant effects on L. decemlineata, while squamocin was toxic to L. decemlineata and M. persicae. Neither acetogenin was mutagenic, although both were toxic in the absence of a metabolic activation system. We compared these results with those obtained with rotenone, a well-known respiratory inhibitor that was highly toxic to L. decemlineata and M. persicae and showed no mutagenicity/toxicity in the S. typhimurium strains tested up to a concentration of 1000 microg per plate.

Animals↗
PubMed2000

Epoxy-acetogenins and other polyketide epoxy derivatives as inhibitors of the mitochondrial respiratory chain complex I.

Annonaceous acetogenins (ACG), an extensive group of cytotoxic natural products, are antitumor agents whose main mode of action is inhibition of the mammalian mitochondrial complex I. Herein we describe the importance of the different chemical groups along the alkyl chain for optimal inhibitory potency, discussing the structurally relevant factors present in these compounds. For this purpose, a series of epoxide derivatives from alpha-linolenic acid were prepared and their activity compared with that of epoxy-acetogenins and tetrahydrofuranic (THF) acetogenins isolated from Rollinia membranacea.

Electron Transport↗
PubMed2000

Hormonal treatment may harm the germ cells in 1 to 3-year-old boys with cryptorchidism.

PURPOSE: Hormonal treatment with human chorionic gonadotropin (HCG) or gonadotropin releasing hormone may be given initially for cryptorchidism. We evaluated whether hormonal treatment is safe for the germ cells in boys with cryptorchidism 1 to 3 years old in whom follicle-stimulating hormone, luteinizing hormone and testosterone values are normally low. MATERIALS AND METHODS: We measured the number of spermatogonia per tubule at orchiopexy in 72 consecutive boys with cryptorchidism who underwent simultaneous testicular biopsy. In 19 patients gonadotropin releasing hormone was unsuccessful, while 8 received HCG and 45 underwent orchiopexy without hormonal therapy. Groups were otherwise equal. RESULTS: Patients who underwent surgery only had a higher number of spermatogonia per tubule than those in whom hormonal treatment was unsuccessful (p<0.05). Spermatogonia per tubule values were normal only after surgery alone (p = 0.06). Gonadotropin releasing hormone and HCG influenced germ cells equally. CONCLUSIONS: In 1 to 3-year-old boys with cryptorchidism gonadotropin releasing hormone or HCG given for testicular descent may suppress the number of germ cells.

Child, Preschool↗