bluuebunny/crossref_metadata_2025 huggingface dataset:
Bone‐impacted fibular free flap: Long‐term dental implant success and complications compared to traditional fibular free tissue transfer
Authors: Barber Brittany R. , Dziegelewski Peter T. , Chuka Richelle , O'Connell Daniel , Harris Jeffrey R. , Seikaly Hadi
Published: December 2015

Background

The purpose of this study was to compare complications and dental implant success between the bone‐impacted fibula free flap (BIFFF) and the traditional fibular free flap used in mandibular and midface reconstruction.

Methods

Retrospective review of all patients undergoing BIFFF or traditional fibular free flap reconstruction from 2001 to 2009 was undertaken. Complications related to the BIFFF and traditional fibular free flap site of reconstruction were compared. Dental implant success rates for each type of flap were compared at 1‐year intervals for 5 years.

Results

One hundred fourteen patients underwent 81 BIFFFs and 35 traditional fibular free flaps. No significant difference in complications between BIFFF (20.9%) and traditional fibular free flap (25.7%) reconstruction was observed. Logistic regression analysis revealed only the site as a predictor of both single and multiple complications. At 5 years postimplantation, dental implant success rates were 95.5% and 77.1% for BIFFF and traditional fibular free flap, respectively (p = .006).

Conclusion

BIFFF reconstruction is a novel surgical technique that may improve long‐term dental implant success rates with no additional risk of complications. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1783–E1787, 2016
Dissolved inorganic carbon evolution in neutral discharge from mine tailings piles
Authors: Ali Hendratta N. , Atekwana Eliot A.
Published: December 2015

We measured the concentrations of dissolved inorganic carbon (DIC) and major ions and the stable carbon isotope ratios of DIC (δ13CDIC) in two creeks discharging from carbonate‐rich sulphide‐containing mine tailings piles. Our aim was to assess downstream carbon evolution of the tailings discharge as it interacted with the atmosphere. The discharge had pH of 6.5–8.1 and was saturated with respect to carbonates. Over the reach of one creek, the DIC concentrations decreased by 1.1 mmol C/l and δ13CDIC increased by ~4.0‰ 200 m from the seep source. The decrease in the DIC concentrations was concomitant with decreases in the partial pressure of CO2(aq) because of the loss of excess CO2(aq) from the discharge. The corresponding enrichment in the δ13CDIC is because of kinetic isotope fractionation accompanying the loss of CO2(g). Over the reach of the other creek, there was no significant decrease in the DIC concentrations or notable changes in the δ13CDIC. The insignificant change in the DIC concentrations and the δ13CDIC is because the first water sample was collected 160 m away from the discharge seep, not accessible during this research. In this case, most of the excess CO2(aq) was lost before our first sampling station. Our results indicate that neutral discharges from tailings piles quickly lose excess CO2(aq) to the atmosphere and the DIC becomes enrich in 13C. We suggest that a significant amount of carbon cycling in neutral discharges from tailings piles occur close to the locations where the discharge seeps to the surface. Copyright © 2015 John Wiley & Sons, Ltd.
Testing the DQP: What Was Learned About Learning Outcomes?
Authors: Ickes Jessica L. , Flowers Daniel R.
Published: December 2015

Through a campuswide project using the Degree Qualifications Profile (DQP) as a comparison tool that engaged students and faculty, the authors share findings and implications about learning outcomes for IR professionals and DQP authors while considering the role of IR in large‐scale, campuswide projects.
New Directions for IR, the DQP, and Tuning
Authors: Jankowski Natasha A. , Marshall David W.
Published: December 2015

This concluding essay provides a glimpse to the future and alerts IR professionals to related initiatives as well as provides an update to ongoing work with DQP and Tuning. Pulling from the prior chapters it provides some implications for IR offices to consider, not only in their work with the DQP and Tuning, but in terms of general decision support.
Pharmacology, Clinical Efficacy and Adverse Effects of Vindesine Sulfate, A New Vinca Alkaloid
Authors: Cersosimo Robert J. , Bromer Richard , Licciardello Jere T. W. , Hong Waun Ki
Published: December 2015

Vindesine is a new vinca alkaloid antineoplastic agent derived from vinblastine. However, its antineoplastic spectrum more closely resembles that of vincristine. Clinical studies indicate activity against acute leukemia, lung cancer, carcinoma of the breast, squamous cell carcinoma of the esophagus and head and neck, Hodgkin's disease and non‐Hodgkin's lymphomas. Pharmacokinetic studies indicate that vindesine exhibits a triphasic elimination pattern with a terminal half‐life of 24.2 hours. Elimination is primarily through hepatic metabolism. The major side effects associated with vindesine therapy are myelosuppression and neurotoxicity. Other side effects include alopecia, nausea and vomiting and local tissue irritation associated with extravasation. Vindesine will be a positive addition to the antineoplastic armamentarium. The full extent of its activity remains to be established.
Effect of Dose and Ointment Application Technique on Nitroglycerin Plasma Concentrations
Authors: Iafrate R. Peter , Yost Richard L. , Curry Stephen H. , Gotz Vincent P. , Caranasos George J.
Published: December 2015

Each of ten non‐smoking, healthy male volunteers between the ages of 20 and 30 and within 10% of their ideal body weight received four nitroglycerin ointment (NTG‐O) treatments: ½″ NTG‐O over 3.94 in2 and 7.88 in2, and 1″ NTG‐O over 3.94 in2 and 7.88 in2 in a randomized order. Eleven blood samples and 22 determinations of heart rate and blood pressure were obtained over each 6‐hour study period. Nitroglycerin plasma concentrations were determined by gas‐liquid chromatography with electron capture detection. Area under the nitroglycerin plasma concentration‐time curve (AUC), peak plasma concentration (Cmax), and time to peak concentration (Tmax) were determined for each study. Cmax and AUC values were corrected for the actual dose applied. Differences between AUC, Cmax and Tmax were tested using repeated measures analysis of variance. Change in surface area had no statistically significant effect on AUC, Cmax and Tmax. Mean AUC for the ½″ and 1″ doses differed (648 vs 2003 ng.ml−1 min, p = 0.016), as did Cmax (4.6 vs 12.4 ng.ml−1, p = 0.022); however, there was no correlation between individual doses and AUCs. Generally, NTG plasma concentrations within the proposed therapeutic range of 1.2–11.1 ng.ml−1 were detectable throughout each study interval. These data suggest that continuous absorption occurred throughout the 6‐hour dosing interval, that a trend toward increased AUC and Cmax occurred with the larger surface area, and that, in general, doubling the dose of NTG‐O doubles the AUC.
Alprazolam in Bipolar‐I Depressions
Authors: Rush A. John , Schlesser Michael A. , Erman Milton , Fairchild Ms. Carol
Published: December 2015

In an open‐label study of alprazolam in five bipolar‐I depressed patients, three patients remitted completely, one failed to respond, and one responded transiently, based on the Hamilton Rating Scale and Beck Depression Inventory scores. Further studies of alprazolam as an antidepressant are warranted.
Complexation versus Hemodialysis To Reduce Elevated Aminoglycoside Serum Concentrations
Authors: Schentag Jerome J. , Simons Gary W. , Schultz Robert W. , Vance John W. , Williams James S.
Published: December 2015

Seven patients with acutely elevated aminoglycoside serum concentrations were studied comparing the effect of hemodialysis (n = 3) with removal by complexation using ticarcillin or carbenicillin (n = 4). Aminoglycoside serum half‐life before intervention averaged 96 hours for the dialysis group and 67 hours for the complexation group. Ticarcillin was used for a minimum of 48 hours, while hemodialysis removal was estimated over 48 hours, which included two 4‐hour dialysis periods. Aminoglycoside serum half‐life was reduced to an average of 11 hours with hemodialysis, while with complexation using ticarcillin, it was reduced to 12 hours.

During the 48‐hour comparison period, complexation removed approximately 50% more aminoglycoside than did hemodialysis, primarily because the improved removal technique was sustained over the entire time. Complexation appears to be as effective as continuous hemodialysis in lowering excessive aminoglycoside serum concentrations. Complexation with ticarcillin can be more rapidly initiated, is less expensive and there is a low risk of adverse reactions. This method provides continued treatment of infections in patients with elevated serum concentrations and/or nephrotoxicity who require cessation of aminoglycoside therapy.
II. A Case for Long‐Term Treatment with Anticonvulsants
Authors: Hodson Andrew
Published: December 2015

Seizures occurring in the neonatal period are one of the most significant discriminating factors in predicting childhood neurologic mortality and morbidity (epilepsy, cerebral palsy and mental retardation). Data derived from retrospective and prospective studies indicate that different variables, such as cause and severity of seizure activity, birth weight, neurologic examination and electroencephalogram, help predict which of these children will be severely affected. Most physicians treat such children with an anticonvulsant (phenobarbital) for the first year of life on the supposition that this therapy will minimize mortality and long‐term morbidity. There are no controlled studies to indicate whether anticonvulsant therapy affects the outcome in children with neonatal seizures. It may now be possible to select those who are at significantly higher risk for neurologic morbidity, and these infants may benefit from anticonvulsant prophylaxis with phenobarbital.
The Consistency of Theophylline Absorption from a Sustained‐Release Formulation in Asthmatic Children
Authors: Hill Malcolm , Haltom James R. , Szefler Stanley J.
Published: December 2015

Theophylline absorption was studied in asthmatic children ages 2–7 years. A bead‐filled capsule of sustained‐release theophylline (Slo‐Bid, William H. Rorer, Inc., Fort Washington, PA) was administered in equal doses twice daily (8 am and 8 pm) to produce serum theophylline concentrations (STCs) between 10 and 20 μg ml. After 7 days, blood samples were obtained every 2 hours for 24 hours. This sequence was repeated after another seven days of treatment. Elimination values were calculated after an intravenous reference dose. Slo‐Bid was completely absorbed (mean ± SD percentage of dose absorbed of 117.1 ± 26.1 on day 1, and 104.8 ± 16.1% on day 2), and the pattern of absorption was consistent from day to day, with maximum STCs occurring 2–6 hours after the dose, and minimum STCs at or near the time of pm dose. The percentage of fluctuation of 149.7 ± 49.7% and 163.0 ± 114.0% (mean ± SD) on days 1 and 2, respectively, was slightly higher than desired, but probably was a result of rapid theophylline clearance in this group of children (119.9 ± 25.8 ml/hr/kg). Mean residence time for absorption after am and pm doses indicated significantly longer time for absorption (t̄a) after the pm doses: mean ± SEM t̄a for am doses on days 1 and 2 was 2.8 ±0.3 and 2.7 ±0.2 hours, respectively, and increased to 3.9 ± 0.3 and 3.7 ± 0.5 hours after pm doses on days 1 and 2, respectively (p<0.0001). Theophylline was absorbed in a consistent pattern with predictable STCs over the 24‐hour study periods. Although slower absorption was observed after pm doses, a temporally related decrease in STCs was not pronounced in this group of young asthmatics.
Follow‐Up Study of Tolmetin Users
Authors: Jick Hershel , Jick Susan S. , Hunter Judith R. , Walker Alexander M.
Published: December 2015

A follow‐up study of 8370 outpatients who filled over 24,000 prescriptions for tolmetin revealed no hospital admissions for acute allergic, blood, skin, or central nervous system illness within 90 days of filling a prescription or refill for the drug. There were two cases of liver disease and two cases of nephrotic syndrome in which an etiologic relationship to tolmetin seemed unlikely but could not be entirely ruled out. In addition, 11 patients were hospitalized for peptic ulcer disease and its complications. In all but two patients other risk factors were present that could readily explain the illness. The rate of hospitalization for peptic ulcer disease and its complications among tolmetin recipients appears to be of the same magnitude as that in patients who take other nonsteroidal antiflammatory drugs in this population, and close to that of the population at large.
Lisinopril: A New Angiotensin‐Converting Enzyme Inhibitor
Authors: Chase Sandra L. , Sutton Jacqueline D.
Published: December 2015

Lisinopril is a synthetic, nonsulfhydryl, angiotensin‐converting enzyme inhibitor. Its bioavailability is approximately 25% and is not affected by food. Hepatic metabolism is not required for pharmacologic effect, which occurs 1 hour after administration. Peak serum concentration and effect are delayed, occurring 6–8 hours after a single dose and lasting for at least 24 hours. The drug is eliminated primarily by the kidneys. The elimination half‐life is 12.6 hours and is prolonged in renal impairment. Lisinopril 10–80 mg once a day is effective in lowering blood pressure in all grades of essential and renovascular hypertension. It is as effective as hydrochlorothiazide, atenolol, metoprolol, and nifedipine. Combining lisinopril with hydrochlorothiazide produces a greater degree of blood pressure reduction. Patients with congestive heart failure have demonstrated immediate and prolonged beneficial hemodynamic effects and increased exercise tolerance. Lisinopril is well tolerated. Clinically significant drug interactions have not been reported, but caution should be used when lisinopril is administered with diuretics, nifedipine, or agents that may increase concentrations of potassium. The usual initial oral dosage of lisinopril is 10 mg once a day (range 20–40 mg/day). Lower dosages may be necessary in patients with renal impairment or congestive heart failure, elderly persons, and those receiving diuretics.
Drug Absorption in Gastrointestinal Disease and Surgery
Authors: Gubbins Paul O. , Bertch Karen E.
Published: December 2015

It is well recognized that drug absorption from the gastrointestinal tract is influenced by gastric and intestinal motility, surface area available for absorption, and physicochemical properties of the drug. Disease and surgery have been shown to alter these factors. Consequently, drug absorption can be altered as well, and these affect drug therapy. Apparently this effect is variable, but the variability may be due in part to the complexities of performing studies in this area. For example, many patient factors as well as drug characteristics must be considered. In addition, appropriate interpretation of results requires that intravenous data be collected if changes in absorption are based on bioavailability. At this time, the alterations in drug absorption due to gastrointestinal disease and surgery are of unknown or little clinical significance; nevertheless, clinicians should be aware that the possibility of malabsorption exists and anticipate any monitoring of or alterations in therapy that may have to be made.
Effect of Hypoxia on Spontaneous Contractions of the Adult Rabbit Isolated Testicular Capsule and Duodenum
Authors: DAVIS JOSEPH R. , HOROWITZ ARTHUR M.
Published: December 2015

Spontaneous contractions of the adult rabbit isolated testicular capsule have been found to adversely affected by short exposures to hypoxia. The data of the present study suggest that acute exposure of the testicular capsule to hypoxia, resulting in a prolonged contracture, may interfere with normal testicular capsular function and possibly sperm transport. The finding that the testicular capsule possesses smooth muscle morphology similar to that of duodenum, but showing an opposite response in tissue tone upon exposure to hypoxia, may further suggest new factors in the stimulus‐contraction coupling process of smooth muscle.
Aging in the AXC Rat: Androgen Regulation of Prostate Prolactin Receptors
Authors: BOESEL ROBERT W. , SHAIN SYDNEY A.
Published: December 2015

Prolactin receptor content of ventral prostates of young mature (4–5‐month‐old), adult (12–13‐month‐old), and aged (24–27‐month‐old) untreated AXC rats was 677 ± 151,826 ± 242, and 213 ± 59 (P < 0.01, aged versus adult or young mature) femtomoles per prostate, respectively. Orchiectomy at 48 hours prior to sacrifice caused an 80% reduction in ventral prostate prolactin receptor content in both young mature and aged rats. Testosterone treatment (2.5 mg/day) of intact rats for two days increased ventral prostate prolactin receptor content 59% in aged rats and 34% in young mature rats. Changes observed in ventral prostate prolactin receptor content could not be attributed to differences in serum prolactin levels, which were identical for the rats in all treatment groups. Significantly, prolactin receptors were not demonstrable in dorsolateral prostate from any of these rats. The results demonstrate that androgen regulation of ventral prostate prolactin receptors in aged AXC rats is qualitatively comparable to that characteristic of ventral prostate of young mature AXC rats. The greater relative increase in prolactin receptor levels in aged rats in response to exogenous testosterone suggests that the marked reduction in prolactin receptors in ventral prostate of intact 24–27‐month‐old rats may be related to lower plasma testosterone concentration.
Nature of the Clearance of Exogenous Testosterone and Progesterone in Ejaculated Bovine Semen
Authors: EILER HUGO , GRAVES CHARLES N.
Published: December 2015

Plasma and semen concentrations of androgens and progestins were not influenced by repetitive ejaculation in bulls. Within 20 minutes after the injection of testosterone (100 mg Intravenously), plasma concentration of androgen (mean ± SEM) was 698 ± 240 ng/ml (92% testosterone) and semen concentration of androgen was 27.7 ng/ml (76% testosterone). Within 20 minutes after the injection of progesterone (100 mg intravenously), plasma concentration of progestin was 2226 ± 635 ng/ml (96% progesterone) and semen concentration of progestin was 68.2 ± 2.2 ng/ml (68% progesterone). Thereafter, the concentrations of androgens and progestins in both plasma and semen steadily declined. Semen/blood concentration ratio values for progestins and androgens were similar to each other during the experimental period. It was concluded that testosterone and progesterone were readily transferred to the ejaculate from the blood.
Prolactin‐induced Modulation of Tissue Growth Rate Patterns in Albino Rats During Puberal Transition
Authors: RAO M. RAMACHANDRA , GOVINDAPPA S.
Published: December 2015

The role of prolactin (PRL) in the puberal transition of male albino rats has been investigated. It was found that PRL elevated total organ growth rates, tissue somatic indices, and dry weights of reproductive and nonreproductive tissues. Analysis of the growth rate patterns of these tissues suggests that PRL induces changes that lead to the initiation of function of the testis and accessory reproductive glands in the prepuberal male rat.
Experimental Unilateral Torsion of the Spermatic Cord in Guinea Pigs Effects on the Contralateral Testis
Authors: CHAKRABORTY JYOTSNA , JHUNJHUNWALA JAGADISH
Published: December 2015

A systematic investigation of the effects of unilateral torsion of the spermatic cord on the contralateral testis of the guinea pig was carried out for variable time periods, ie, seven days, one, three and six months. Both histological and ultrastructural studies were made on all testicular autopsy materials collected from five groups of animals. Those five groups were: group I, 12 animals with unilateral torsion induced and maintained until the day of sacrifice; group II, 12 animals with unilateral torsion induced for four hours; group III, eight sham‐operated animals; group IV, eight pentobarbital injected animals; group V. four untreated control animals. Of 24 group I and group II animals, degenerative changes were noticed in the contralateral testis in ten animals. Those changes ranged from spermatid and spermatocyte degeneration to the complete loss of all types of germ cells in the contralateral testis. The degree of damage seemed to correlate with the severity of damage in the torsion‐side testis and the length of time the damaged testis was retained in the body. It was concluded that a damaged testis retained in the body may cause degenerative changes in the contralateral testis.
Preparation of Epithelial and Stromal Cell Fractions from Immature Rat Prostatic Tissue Using Percoll Gradients
Authors: ORLOWSKI JOHN , BIRD CHARLES E. , CLARK ALBERT F.
Published: December 2015

A method is described for the dispersion, isolation, and partial characterization of epithelial and stromal tissue cells from the rat ventral prostate. Viable epithelial and stromal cells have been prepared from a collagenase and trypsin digest of immature rat ventral prostates. This mixed population of cells was fractionated on two continuous Percoll (a modified colloidal silica) gradients to give an epithelial‐enriched fraction and a stromal‐enriched fraction (greater than 90% enrichment for each fraction). Cells were viable as demonstrated by exclusion of trypan blue dye and by their ability to metabolize testosterone. Acid phosphatase activity, a marker of androgen action in rat ventral prostate, was found predominantly in the epithelial cell fraction. This cell separation procedure provides a simple, rapid, and reproducible method for the isolation of prostatic epithelial and stromal cells that will be used for studies of androgen‐mediated differentiation in rat prostate as it relates to changes in acid phosphatase activity. Separation of these different cell types should also permit investigation of some of their metabolic interactions.
Sperm Morphology Assessment as an Indicator of Human Fertilizing Capacity
Authors: ROGERS B. JANE , BENTWOOD BARBARA J. , VAN CAMPEN HANA , HELMBRECHT GARY , SODERDAHL DOUGLAS , HALE RALPH W.
Published: December 2015

Semen samples from 95 men were examined by routine semen analysis and specific histologic staining for sperm morphology. The men were classified into fertile and infertile groups on the basis of clinical evaluation and in vitro testing, using the zona‐free hamster egg penetration assay. Thirty men were designated as fertile, as they had fathered children and their sperm showed penetration of greater than 20% of the zona‐free hamster eggs with the in vitro fertilization test. Subjects classified as infertile were men from infertile couples whose wives showed no evidence of infertility and whose in vitro fertilization ability was 10% or less. The semen analysis parameters of the fertile and infertile groups were significantly different. Fertile men had mean values of 108 ± 106 sperm/ml, 61% motile, 64% normal forms (sperm with oval morphology), and 69% penetration in vitro. The mean values for infertile men were significantly lower: 42 ± 106 sperm/ml, 45% motile, 32% normal forms, and 3.2% penetration in vitro. The importance of the morphology parameter was revealed by comparison of the percentage of penetration with count, motility, and morphology. Penetration correlated best with morphology (r = 0.730) as compared with motility (r = 0.451) and count (r = 0.605). The distribution of abnormalities in the infertile group revealed 81.6% with abnormal morphology (<50%), 53.8% with abnormal motility (<50%), and 38.5% with abnormal count (<20 million/ml). As a single parameter, decreased number of normal forms appears to be a good indicator for clinical infertility if in vitro fertilization testing is not available.
Animal Model of Isolated Gonadotropin Deficiency I. Hormonal Responses to LHRH Immunoneutralization
Authors: SCHANBACHER BRUCE D. , ENGLISH HUGH F. , GROSS DOUGLAS , SANTEN RICHARD J. , WALKER MICHAEL F. , FALVO RICHARD E.
Published: December 2015

Five intact male mongrel dogs, characterized by an episodic secretory pattern of LH and normal serum testosterone concentrations, were actively immunized against LHRH by subcutaneous injections of 200 μg of a LHRH‐human serum albumin conjugate at 0, 4, and 8 weeks. After 12 weeks, two dogs having the highest antibody titers to LHRH (25% and 51% binding of 125I‐LHRH in serum diluted 1:1000 B/Bo) had low to nondetectable serum concentrations of LH and testosterone, whereas serum FSH concentrations were significantly reduced in only one of these dogs. Immunocytochemical techniques showed that the pituitaries of these same two dogs had smaller and fewer LH immunoreactive gonadotropes than did the pituitaries of another three immunized‐nonaffected dogs or of the five nonimmunized control dogs. The two LHRH‐immunized dogs characterized by hypogonadotropism also had reduced testis (4.0 and 4.0 g) and prostate (2.1 and 1.7 g) weights when compared to control dogs (testis: 12.1 ± 1.0 g and prostate: 9.2 ± 1.9 g). LHRH antibody titers in three immunized dogs were demonstrable (8.1, 9.8, and 14.2% B/Bo), but effects on LH, FSH, and testosterone concentrations, pituitary gonadotropes, and reproductive tissue weights were not apparent. The similarity in hormonal and tissue responses observed between dogs effectively immunized against LHRH and men with isolated gonadotropin deficiency suggests mat the LHRH‐immunized dog may provide a suitable experimental model for the study of patients with isolated gonadotropin deficiency.
Effect of Gossypol on Testicular Testosterone Production In Vitro
Authors: KALLA NATWAR R. , WEINBAUER G. F. , ROVAN E. , FRICK J.
Published: December 2015

Testicular minces were utilized to study the effect of gossypol on testosterone production. Testosterone production was assessed in both control and gossypol treated groups after 0 to 4 hours incubation in the presence of hCG. Media testosterone was measured by radioimmunoassay. Gossypol did not alter testosterone production when present in incubates at the concentrations of 3.5 × 10−5M, 7 × 10−5M and 3.5 × 10−4M. Preincubation of testis mince with gossypol (7 × 10−6M, 7 × 10−5M, 3.5 × 10−4M) for 1 to 4 hours did not alter subsequent hCG induced testosterone production in mature rats. Testosterone production however, was inhibited in immature rat testis when the whole testis was incubated for 4 hours with different concentrations of gossypol (7 × 10−6M, 7 × 10−5M, 3.5 × 10−4M). In vivo testosterone production was not inhibited in the immature rat testis 24 hours after oral administration of gossypol (100 mg/kg).
Growth and Reproductive Adaptation in Male Rats with Chronic Protein Deficiency
Authors: GLASS ALLAN R. , ANDERSON JEFFREY , HERBERT DAMON , VIGERSKY ROBERT A.
Published: December 2015

In previous studies, male rats fed a low‐protein diet beginning at weaning were found to have impaired sexual development through age 11 weeks when compared to food‐restricted, weight‐matched controls fed a diet with normal protein content. To determine whether male rats show long‐term adaptation of the reproductive axis to low‐protein feeding, we assessed sexual maturation and growth in rats fed a low protein (9%) diet from weaning until sacrifice at various points in time between ages 79 and 185 days. After age 80 days, there was no difference in reproductive organ weights (prostate, seminal vesicles, testis) or serum hormone levels (luteinizing hormone, follicle stimulating hormone, testosterone) between protein‐deficient animals and food‐restricted weight‐matched controls given a normal diet. In addition, there was no difference between protein‐deficient animals and controls in indices of linear growth (naso‐anal and tail length) or fatness (Lee index). We conclude that both growth and reproductive function of male rats show adaptation to long term feeding of a low‐protein diet.
The Role of Endogenous Opioid Peptides in the Control of Androgen Levels in the Male Nonhuman Primate
Authors: GILBEAU PAMELA M. , ALMIREZ RAMONA G. , HOLADAY JOHN W. , SMITH CAROL GRACE
Published: December 2015

Plasma androgen levels studied following the injection of the opioid agonists morphine sulfate (0.5–1.0 mg/kg), β‐endorphin (10–20 mg/kg), and [D‐Ala2, D‐Leu5]‐enkephalin (DADLE; 5–20 μg/kg), and the opioid receptor antagonist naloxone (0.5–2.0 mg/kg) in nonrestrained adult male rhesus monkeys. Drugs were administered and blood samples were collected through indwelling jugular catheters. Morphine (1.0 mg/kg) and DADLE (10.0 μg/kg) decreased androgen levels by 70% and 34%, respectively. Significant decreases occurred 80 minutes after drug injections, and levels remained depressed for 180 minutes; β‐endorphin (20 μg/kg) produced no effect on androgen levels. Treatment with naloxone (0.5 mg/kg‐2.0 mg/kg) alone produced marked increases in androgen levels. Peak hormone levels occurred 80 minutes after naloxone administration and remained elevated for up to 2 hours. The depressant effects of morphine and DADLE on androgen levels were completely reversed by the administration of naloxone (1.0 mg/kg). In monkeys pretreated with hCG, neither morphine (1.0 mg/kg) nor DADLE (20 μg‐kg) had any effect on androgen levels for up to 3 hours after opioid administration. Administration of morphine or endogenous opioid peptides exerts negative effects on androgen levels, whereas antagonism or endogenous or exogenous opiates by naloxone results in increases in circulating androgens. These results support a physiologic role of the endogenous opioid peptides in primate reproductive function.
Daily and Alternate‐day Treatment with an LHRH Analog in the Therapy of Idiopathic Hypogonadotropic Hypogonadism
Authors: LOMBARDI G. , DE ROSA M. , TORINO G. , QUAGLIOZZI L. , AURIGEMMA A. C. , PANZA N.
Published: December 2015

Twenty‐five male patients with idiopathic hypogonadotropic hypogonadism were treated with 5μg of an LHRH analog (D‐Leu6‐Des‐Gly10‐LHRH‐ethylamide) intramuscularly for one month. The FSH and LH responses (quantitated as cumulative response areas) to acute LHRH intravenous administration (100 μg) were evaluated before and after each week of treatment. The patients were randomly divided into two groups: group A (16 patients) was treated every day; group B (nine patients) was treated every other day. Each group was divided into two subgroups (1 and 2), according to the degree of pretreatment LH response impairment. Patients in the first subgroup had a pretreatment cumulative response area greater than 3 SD below the mean for normal males. Patients in the second subgroup had a response less than 3 SD below the mean for normal males.

Daily treatment produced a significant and progressive increase in LH response in subgroup A‐1, but in the second subgroup (A‐2) there was a maximal increase after the first and second week, with a subsequent decline. Alternate‐day treatment, on the other hand, produced a significant and progressive increase in LH response in all patients from subgroups B‐1 and B‐2.

Both daily and alternate‐day treatments induced an initial increase in FSH response during the first week, followed by a progressive decline in all the groups. Finally, there was a lack of response to either form of treatment with regard to testosterone secretion and spermatogenesis.

The findings indicate that LH response to LHRH analog differed depending on the degree of pretreatment pituitary impairment and the course of therapy followed.
Acute Experimental Testicular Torsion: No Effect on the Contralateral Testis
Authors: TURNER T. T.
Published: December 2015

Other investigators have shown that chronic unilateral testicular torsion produces negative effects on the contralateral testis in experimental animals. In the present study, bilateral testicular weight and histology, and concentrations and motility of spermatozoa from the cauda epididymidis were studied after 0 to 4 hours of acute unilateral testicular torsion in the rat. The obstruction of blood flow by torsion was documented, as well as the presence or absence of return blood flow after the relief of torsion. The above mentioned parameters of testicular function were studied at 7, 30, and 60 days after relief of torsion. Ipsilateral testis weights and epididymal sperm concentrations and motility were significantly reduced by 1, 2, and 4 hours of torsion. The histology of torsioned testes was also severely altered, and no seminiferous epithelial repair was evident 60 days after torsion. Contralateral testicles were not affected by ipsilateral torsion of 1, 2, or 4 hours duration, despite the fact that the ipsilateral testis function was completely compromised by 2 and 4 hours of torsion. These results indicate that there would be no clinical benefit in removing the acutely torsioned testis of Sprague–Dawley rats since it poses no threat to the contralateral testis.
Response to Acute hCG Stimulation and Steroidogenic Potential of Leydig Cell Fibroblastic Precursors in Humans
Authors: CHEMES H. E. , GOTTLIEB S. E. , PASQUALINI T. , DOMENICHINI E. , RIVAROLA M. A. , BERGADÁ C.
Published: December 2015

The process of early testosterone (T) secretion and Leydig cell differentiation in humans was studied to explore the steroidogenic capacity of Leydig cell fibroblastic precursors. Seven cryptorchid boys received hCG prior to orchidopexy. Patients CP, PB, and MR received one injection of 1000 IU; patients JR and GG, three daily injections of 1000 IU, and patients MP and MM, five daily injections of 1000 IU. A testicular biopsy was obtained at the time of operation, 24 hours after the last injection. Serum T (ng/dl) before and after hCG stimulation and testicular T (ng/g) were determined by RIA. A control prepubertal testis (tumoral orchidectomy) was incubated in vitro and showed a time‐dependent accumulation of T both in the medium and the testicular tissue. Testosterone released into the medium at 1, 2, and 4 hours was 0.76, 1.43, and 4.03 ng/ml, respectively. Tissue T at 0, 1, 2, and 4 hours was 9, 11, 16, and 24 ng/g, respectively. This indicates synthesis and secretion of T into the medium. Control testes showed abundant fibroblastic precursors with scanty cytoplasm, few organelles, heterochromatic nuclei, and minute nucleoli. No Leydig cells were present. After 1 day of hCG stimulation, numerous fibroblasts were activated, displaying enlarged cytoplasms with increased numbers of organelles, nuclei rich in euchromatin, and bigger nucleoli. No Leydig cells were present. Basal serum testosterone was 58.2 ± 45.3 ng/dl and 87.3 ± 42.0 after hCG administration, while testicular T was 974.0 ± 686.0 ng/g (control prepubertal testicular T is 10–50 ng/g). After 3 days of hCG, activated fibroblasts increased and immature Leydig cells appeared. Basal serum T was 35.5 ± 7.8 ng/dl and 394.0 ± 24.0 after hCG stimulation, while testicular T rose to 2797.5 ± 1222.6 ng/g. After 5 days, mature Leydig cells appeared for the first time. Serum T was 58 ± 59.3 ng/dl (basal) and 641.5 ± 390 ng/dl (after hCG); testicular T was 789 ng/g (patient MM did not have a value for testicular T). HCG induced numerous coated pits and endocytic vesicles in activated fibroblasts and young Leydig cells, suggesting receptor aggregation and internalization of hormone‐receptor complexes. Peroxidase‐antiperoxidase (PAP) localization of T was positive in peritubular fibroblasts and Leydig cells. These results demonstrate the following: 1) that early phases of hCG stimulation are characterized by a very precocious rise in testicular testosterone production, the activation of peritubular fibroblasts, and subsequent Leydig cell differentiation, and 2) that fibroblastic precursors and activated fibroblasts are steroidogenically active, as shown by the PAP localization, in vitro T secretion, and early rise in testicular testosterone before the appearance of mature Leydig cells.
Sertoli Cell Junctional Complexes in Gossypol‐treated Neonatal and Adult Guinea Pigs
Authors: PELLETIER R.‐MARC , FRIEND DANIEL S.
Published: December 2015

The effect of gossypol, an experimental male contraceptive agent, on the development and maintenance of the blood‐testis barrier was determined by feeding gossypol daily to prepubertal and adult guinea pigs, and then examining their testes by electron microscopy of thin sections and freeze‐fracture replicas. In guinea pigs of 10 to 30 and 10 to 40 days of age that were fed gossypol, impermeable continuous junctional zones did not develop between adjacent Sertoli cells. Compartmentalization of germ cells in the seminiferous epithelium, therefore, was nonexistent. These findings were obtained by use of the sterol‐binding polyene, filipin, used as a low molecular weight tracer in combination with freeze‐fracture. In general, the seminiferous tubules lacked lumina and spermatogenesis did not progress beyond the pachytene spermatocyte stage. In adult guinea pigs fed gossypol daily for five weeks, continuous zonules at the base of the seminiferous epithelium appeared intact and were impermeable to filipin. Discontinuous zonules found higher in the epithelium showed distensions between interrupted junctional strands and were permeated by filipin. In addition, vacuolated spaces between Sertoli cells and clumps of heterochromatin were conspicuous in some of the Sertoli cell nuclei. Spermatogenesis was disturbed in about 10% of the seminiferous tubules examined. These perturbations included exfoliation of round and elongated spermatids with concomitant formation of multi‐nucleated giant cells. Spermatozoa from these adult male guinea pigs were immotile. These findings suggest that, in neonatal animals, gossypol appears to prevent the maturation of Sertoli cells and this effect is expressed as the failure of focal Sertoli cell tight junctional strands to assemble into continuous zonules. In adult animals, gossypol appears to have no effect on the maintenance of the blood‐testis barrier.
Morphometric Analysis of Spermatozoa in the Assessment of Human Male Fertility
Authors: KATZ DAVID F. , OVERSTREET JAMES W. , SAMUELS STEVEN J. , NISWANDER PAUL W. , BLOOM TODD D. , LEWIS ERNEST L.
Published: December 2015

A videomicrographic system was developed for measurement of morphometric parameters of human spermatozoa. Contours of the images of spermatozoa on a video monitor are digitized by manually tracing them with the cursor of an electromagnetic digitizer integrated to a microcomputer. The accuracy and precision of the methodology were evaluated. A comparison of human sperm heads in shallow wet preparations and in dried, stained preparations indicated that the latter were smaller in length, width, projected area, and circumference, but that the ratio length/width was not different. An analysis was made of 457 ejaculates from 16 fertile donors. The variation between ejaculates within donors was similar in magnitude to the variation between donors. A study was performed comparing seminal sperm morphometry in single specimens from 30 fertile and 30 infertile men. The sperm head length/width ratio was the parameter that differed the most between these two groups. Moreover, it was the per‐ejaculate variability of this parameter, rather than the central tendency, that maximized the difference.
Vitamin A Modifies the Glycopeptide Composition of Cultured Sertoli Cells
Authors: GALDIERI M. , NISTICÒ L.
Published: December 2015

Sertoli cells obtained from prepubertal rat testes were cultured in the presence or absence of retinol. Incorporation of monosaccharides and glycopeptide composition of the cells were studied under two experimental conditions. The results indicate that retinol increases the amount of mannose and glucosamine incorporated into cellular glycoconjugates. The labeled glycopeptides obtained from control and retinol‐treated cells were separated by size and lectin affinity. Gel filtration analysis showed no size differences between the glycopeptides obtained from control and vitamin A‐treated cells. Affinity chromatography on Concanavalin A and Wheat Germ Agglutinin of 3H‐mannose‐labeled glycopeptides showed that Sertoli cells cultured in the presence of retinol contain a higher percentage of high mannose‐type glycopeptides compared with control cells. The effect of retinol on Sertoli cell glycopeptide composition is partially reversed by the administration of FSH.
Transferrin‐Mediated Transcellular Transport of 59Fe Across Confluent Epithelial Sheets of Sertoli Cells Grown in Bicameral Cell Culture Chambers
Authors: DJAKIEW DANIEL , HADLEY MARK A. , BYERS STEPHEN W. , DYM MARTIN
Published: December 2015

The transferrin‐mediated transcellular transport of 59Fe across confluent epithelial sheets of Sertoli cells grown on Millipore filters was investigated. These filters had been impregnated with reconstituted basement membrane and suspended in bicameral (two houses) culture chambers. After five days of culture, Sertoli cells from 10‐day‐old rats formed basally‐located tight junctional complexes. Concomitantly, there was an increase in electrical resistance and the epithelial sheet became impermeable to lanthanum nitrate. The rate of passage of [3H]inulin across the epithelial sheet was considerably less than passage across a filter alone, a filter impregnated with reconstituted basement membrane or an epithelial sheet pretreated with 2 mM EGTA. We conclude from these permeability studies that the tight junctional complexes between Sertoli cells formed an effective transepithelial permeability barrier. Following addition of human serum [59Fe]transferrin to media bathing the basal cytoplasm of the cells, rat testicular [59Fe]transferrin was immunoprecipitated from apical media overlying the Sertoli cells. Cross‐reactivity of the rabbit anti‐rat transferrin antibody with human serum transferrin was less than 0.001%. Substitution of the primary antibody with normal rabbit serum reduced the amount of immunoprecipitable rat testicular [59Fe]transferrin to 20% of normal levels. Prior fixation of the Sertoli cell epithelial sheet in 2.5% glutaraldehyde, addition of a 100‐fold excess of holotransferrin to the basal media, and incubation of the Sertoli cell epithelial sheet at 4 C all reduced the immunoprecipitable rat testicular [59Fe]transferrin in apical media to levels below that for the non‐specific binding of the primary antibody. From these studies we conclude that 59Fe is shuttled across Sertoli cells by two different forms of transferrin. Serum transferrin delivers the 59Fe to the basal cytoplasm of the Sertoli cells. The 59Fe dissociates from the serum transferrin, is delivered to testicular transferrin, and is subsequently secreted from the apical surface of the epithelial sheet of Sertoli cells as testicular [59Fe]transferrin.
Effects of Cyclophosphamide on Selected Cytosolic and Mitochondrial Enzymes in the Epididymis of the Rat
Authors: TRASLER JACQUETTA M. , ROBAIRE BERNARD
Published: December 2015

The anticancer and immunosuppressive drug cyclophosphamide is extensively used in clinical practice and is known to alter fertility in man. We showed previously that treatment of male rats with low daily doses of cyclophosphamide over a 9‐week period caused fetal malformations, a high rate of postimplantation loss and affected epididymal and sperm histology. In the present study, five biochemical measures of epididymal function were used to characterize further the effects of cyclophosphamide on the epididymis. For 1, 3, 6, or 9 weeks, adult Sprague—Dawley rats were gavage‐fed daily with saline (control), 5.1 (low dose), or 6.8 (high dose) mg/kg of cyclophosphamide. The specific activities of the two glycolytic enzymes aldolase and lactate dehydrogenase (LDH), the mitochondrial enzyme succinate dehydrogenase, the cytosolic enzyme carnitine acetyltransferase and the lysosomal enzyme acid phosphatase were determined in cytosolic and mitochondrial subcellular fractions from four segments of the epididymis. Cyclophosphamide caused decreases in protein concentrations in all segments of the epididymis only after 6 weeks of treatment with the high dose. The specific activities of aldolase, LDH and succinate dehydrogenase did not differ from control with respect to dose or duration of treatment. In contrast, there were significant effects of cyclophosphamide on carnitine acetyltransferase and acid phosphatase specific activity. After 1 week of treatment, there was a transient dose‐related decrease in the specific activity of carnitine acetyltransferase, which was most striking for the corpus epididymidis (76% of control), but which did not differ from control after 3, 6, and 9 weeks. After 6 weeks of treatment with the high dose of cyclophosphamide, carnitine acetyltransferase specific activity in the initial segment and the corpus epididymidis was elevated to 165 and 140%, respectively, as compared with the 1‐week high dose values. The specific activity of acid phosphatase did not differ from control after 1 and 9 weeks of treatment. At 3 and 6 weeks, however, there was a dose‐related increase in acid phosphatase specific activity for all regions of the epididymis that was most marked in the cauda after the 6‐week treatment (140% of control). Therefore, low dose, daily treatment of male rats with cyclophosphamide not only alters specific enzymes in specific segments of the epididymis, but acts in a dose‐ and time‐dependent manner. It is possible that these changes could be mediated by direct, toxic effects of the drug on the epithelium or be secondary to alterations in the spermatozoa as a result of the treatment.
Characterization and Localization of β‐Adrenergic Receptors in Control and Cryptorchidized Rat Testis by In Vitro Autoradiography
Authors: TOLSZCZUK M. , FOLLÉA N. , PELLETIER G.
Published: December 2015

β‐adrenergic receptors were localized and characterized in control and cryptorchidized rats to investigate further their role in testicular function. Slide‐mounted cryostat sections were incubated with [125I]cyanopindolol, a specific ligand for β‐adrenergic receptors. The subtypes were characterized by the displacement of [125I]cyanopindolol binding by practolol, which binds preferentially to the β1 subtype, and zinterol, which is preferential for β1 receptors. Labeling was detected by autoradiography, first by exposing sections to Ultrofilm (LKB) and second by dipping slides in NTB‐2 Kodak photographic emulsion. The histologic distribution of receptors was analyzed by counting silver grains overlying the testicular structures. It was found that the vast majority of receptors were of the β2‐subtype. In intact rats, the greatest density of receptors was found in interstitial cells, with some specific labeling over the seminiferous tubules. However, in cryptorchidized animals, the proportion of β2 receptors in tubules that contained mainly Sertoli cells appeared to be markedly increased. The results obtained suggest that catecholamines have multiple sites of action in the testis.