bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapeutic Update on Glycopeptide and Lipopeptide Antibiotics
Authors: Rotschafer John C. , Garrison Mark W. , Rodvold Keith A.
Published: December 2015

Glycopeptide antibiotics in the form of vancomycin have been available for almost 30 years. In the past, vancomycin usually was reserved as an alternative agent to treat staphylococcal and streptococcal infection in patients with a penicillin allergy or hemodialysis shunt infection. With the increasing frequency of both methicillin‐resistant Staphylococcus aureus and Staphylococcus epidermidis, now it is often used as a first‐line agent. Over a 10‐year period, vancomycin sales have increased by almost $1 hundred million. Several new glycopeptide and lipopeptide antibiotics are in various stages of evaluation. While vancomycin resistance to date is a rare phenomenon, these drugs represent a potentially more potent and safer antibiotic alternative to vancomycin. Teicoplanin and daptomycin are two of these investigational agents.
Systemic Absorption of Topical Lidocaine in Elderly and Young Adults Undergoing Bronchoscopy
Authors: Ameer Barbara , Burlingame Mark B. , Harman Eloise M.
Published: December 2015

This study compared the systemic absorption of topically administered lidocaine in elderly and young adult patients who were undergoing fiberoptic bronchoscopy. Fourteen elderly subjects aged 60–72 years (mean 67 yrs) and five young subjects age 31–48 years (mean 42 yrs) were compared with respect to dosage requirements to achieve satisfactory local anesthesia, rate and extent of lidocaine systemic absorption, plasma drug levels, elimination half‐life, and drug side effects. Blood samples were drawn prior to, during, and for an average of 3 hours after the completion of bronchoscopy. Lidocaine plasma concentrations averaged in the range of 3.04–0.88 μg/ml from the beginning of the procedure to the end of blood sampling. Despite high cumulative amounts of 19 mg/kg (1200 mg) of lidocaine administered topically, the regimen proved relatively safe and achieved satisfactory anesthesia. In patients without known risk factors either for delayed hepatic lidocaine clearance or for enhanced mucosal absorption, the regimen is suitable for both young and old individuals.
Angiotensin‐Converting Enzyme Inhibitor‐Induced Cough
Authors: Hume Anne L. , Murphy John L. , Lauerman Scott E.
Published: December 2015

A 65‐year‐old woman started taking enalapril 2.5 mg daily for hypertension. Twelve days later she complained of a persistent, dry cough. Due to the coughing and a preexisting cystocele, she developed stress incontinence and a marked decline in her functional status. The coughing and incontinence resolved with the discontinuation of enalapril. During a subsequent hospitalization the patient received Captopril 6.25 mg twice daily for congestive heart failure. Within 24 hours the dry cough recurred. It resolved with the discontinuation of the drug. Cough is a symptom that is generally not recognized as a drug side effect. However, increasing numbers of case reports document angiotensin‐converting enzyme inhibitor‐induced cough. Although the actual frequency and mechanism are currently unknown, the dry cough typically begins early in the course of therapy. It may be specific to this pharmacologic class rather than to one individual agent. Age and sex may be contributing factors. While cough has been considered a minor side effect, unnecessary hospitalizations and inappropriate treatments may easily result. Even minor adverse reactions may have an impact on a patient's quality of life.
A Comparison of Wax Matrix and Microencapsulated Potassium Chloride in Relation to Upper Gastrointestinal Illness Requiring Hospitalization
Authors: Jick Hershel , Jick Susan S. , Walker Alexander M. , Stergachis Andy
Published: December 2015

The frequency of hospitalization for documented upper gastrointestinal illness among recipients of either wax matrix or microencapsulated potassium chloride was similar in a study in which clinics were randomly assigned to dispense one or the other preparation. The results indicate that there is no material difference between the two preparations in relation to serious upper gastrointestinal illness.
Research in Basic Science Influence of Endotoxin‐Induced Fever on the Pharmacokinetics of Theophylline in the Rabbit Model
Authors: Prince Randall A. , Johnson Jeanine A. , Weinberger Miles M.
Published: December 2015

To assess fever‐induced changes in theophylline pharmacokinetics in the rabbit model, six healthy, male, New Zealand white rabbits were studied using a randomized, matched‐pair design. In treatment 1,15 mg/kg of theophylline was infused into the left marginal ear vein, and several blood samples were collected from the opposite ear for 10 hours. Treatment 2 was conducted in an identical manner, except 20 to 40 μg/kg of Escherichia coli endotoxin was injected into the left marginal ear vein to induce fever. The majority of the rabbits had slight decreases in the slowest disposition rate constant and increases in the volume of distribution at steady state; however, total body clearance was only minimally (5%) changed. No statistically significant differences were noted between these values (Hotelling T2 = 0.32). Given the sample and methods, fever apparently does not affect theophylline pharmacokinetics.
Dopamine and Dobutamine in Pediatric Therapy
Authors: Bhatt‐Mehta Varsha , Nahata Milap C.
Published: December 2015

Dopamine hydrochloride is widely used to increase blood pressure, cardiac output, urine output, and peripheral perfusion in neonates, infants, and older children with shock and cardiac failure. Its pharmacologic effects are dose dependent, and at low, intermediate, and high dosages include dilation of renal, mesenteric, and cerebral vasculature; inotropic response in the myocardium; and increases in peripheral and renal vascular resistance, respectively. The inotropic response is diminished in neonates compared with older children and adults due to maturational differences in norepinephrine stores. The clearance of dopamine varies widely in the pediatric population, depending on age. Its elimination half‐life is approximately 2 minutes in full‐term neonates and older children, and may be as long as 4–5 minutes in preterm infants. Due to immaturity of the autonomic nervous system, the drug may produce some adverse respiratory responses at high dose in neonates, the most common being tachycardia and cardiac arrhythmias. Dobutamine resembles dopamine chemically and is an analog of isoproterenol. It is relatively cardioselective at dosages used in clinical practice, with its main action being on β1adrenergic receptors. Unlike dopamine, it does not have any effect on specific dopaminergic receptors. Dobutamine is used to increase cardiac output in infants and children with circulatory failure. Its elimination half‐life is about 2 minutes in adults and older children. No information is available about its pharmacokinetics in neonates and infants. Adverse effects such as an increase in heart rate usually occur at high dosages.
Management of Allergic Rhinitis: Focus on Intranasal Agents
Authors: Dushay Miriam E. , Johnson Cary E.
Published: December 2015

The clinical manifestations of allergic rhinitis are the result of an immune‐mediated process after exposure of a sensitized individual to airborne allergens. The primary symptomatology includes nasal congestion, rhinorrhea, nasal and conjunctival pruritus, and sneezing. Principles of management include allergen avoidance, palliative therapy, immunotherapy, and pharmacotherapy. Oral decongestants stimulate α‐adrenergic receptors in the nasal cavity, resulting in vasoconstriction and decreased edema. Oral antihistamines block histamine1 (H1) receptors, and may relieve rhinorrhea, sneezing, and nasal and conjunctival pruritus. Topical decongestants have a local effect on adrenergic receptors in the nasal mucosa, resulting in rapid, marked vasoconstriction. Intranasal corticosteroids inhibit mediator release from mast cells and basophils, and reduce edema of the nasal mucosa. Dexamethasone sodium phosphate, beclomethasone dipropionate, and flunisolide are currently available for intranasal administration. Cromolyn sodium inhibits allergen‐induced degranulation and mediator release from sensitized cells, and is useful primarily as a prophylactic agent. Several agents, including the corticosteroids budesonide and flucortin butylester, the mast cell‐stabilizing agent nedocromil sodium, the antichololinergic agent ipratropium bromide, and the H1 receptor antagonist levocabastine are being investigated for intranasal use in the management of allergic rhinitis.
The Effect of Sucralfate Pretreatment on the Pharmacokinetics of Ciprofloxacin
Authors: Nix David E. , Watson William A. , Handy Lanae , Frost R. Wayne , Rescott Denise L. , Goldstein Harvey R.
Published: December 2015

Based on the results of our study of norfloxacin‐sucralfate coadministration, we suspected that sucralfate would interact also with ciprofloxacin if the drugs were administered concurrently. Therefore, we decided to give a 1‐g dose of sucralfate at 6 and 2 hours before a single 750‐mg dose of ciprofloxacin and evaluate its effect on the bioavailability of ciprofloxacin. Twelve healthy, male volunteers received ciprofloxacin alone and with sucralfate pretreatment in a randomized, balanced, crossover design. Blood and urine samples were collected over 24 hours after ciprofloxacin administration, and drug concentrations were assayed by high‐performance liquid chromatography. When sucralfate was given at 6 and 2 hours before ciprofloxacin, an average 30% decrease in ciprofloxacin's bioavailability was noted (p < 0.05). Four of the 12 subjects, however, had decreases in the agent's area under the curve of more than 50% with sucralfate pretreatment. The results of this study suggest that ciprofloxacin and sucralfate should not be administered concurrently until a dosing interval is found that will avoid this potential interaction.
Role of Hyaluronidase in Fertilization: The Antifertility Activity of Myocrisin, a Nontoxic Hyaluronidase Inhibitor
Authors: REDDY JAKKIDI M. , JOYCE CATHY , ZANEVELD LOURENS J. D.
Published: December 2015

Myocrisin, a hyaluronidase inhibitor of low molecular weight, was tested for antifertility activity. In addition, the effect of myocrisin on penetration of the follicle cell layer by spermatozoa was studied. Myocrisin prevented the In vitro fertilization of capacitated mouse spermatozoa when these were added to intact oocytes. The inhibitor had no effect on sperm motility at the concentrations used for the/n vitro fertilization tests, and did not inhibit the acrosome reaction of guinea pig spermatozoa. Myocrisin also had no effect on human acrosin. Fertility was not prevented when the myocrisin‐treated spermatozoa were added to oocytes from which the follicle cell layer had been removed, showing that sperm hyaluronidase is essential specifically for sperm penetration through this ovum investment, at least in the case of the mouse. Myocrisin is approved for human use by the FDA and is a compound worth further In vivo evaluation as a contraceptive.
Effects of Human Chorionic Gonadotropin, Prolactin, and Bromocriptine on Photoperiodinduced Testicular Regression and Recrudescence in Golden Hmsters
Authors: BARTKE A. , HOGAN M. P. , CUTTY C. B.
Published: December 2015

Exposure of adult male hamsters to short day‐length (short photoperiod) causes atrophy of their reproductive systems. Hamsters were transferred from long to short photoperiod and, starting two months later, injected three times a week for three weeks with saline, 1.25, 5, or 20 IU of human chorionic gonadotropin (hCG). Treatment with 5 or 20 IU hCG resulted in significant increases in the weights of the testes and the seminal vesicles. In another group of animals, identical doses of hCG were injected starting at the time of transfer from long to short photoperiod. After 14 weeks of treatment, testicular weight was significantly greater in animals given 20 IU hCG than In animals injected with saline, although it approximated only 50% of testicular weight In adult males kept in long photoperiod. Since we have previously obtained very similar results using prolactin (PRL) producing ectopic pituitary homografts, it was of interest to examine the interaction of pituitary grafts and hCG. Male hamsters were transferred to a short photoperiod and treated with a transplant of one pituitary from an adult female hamster plus 5 IU hCG three times a week or with hCG alone. After 15 weeks, the weights of the testes and the seminal vesides were significantly greater In grafted hCG‐treated hamsters than in those animals treated with hCG only. Testicular weight in animals given both grafts and hCG corresponded to approximately 75% of testicular weight in long photoperiod controls, while seminal vesicle weights in these two groups did not differ.

To examine the role of endogenous PRL in long photoperiod‐induced testicular recrudescence, hamsters which had been exposed to a short photoperiod for two months were returned to a long photoperiod and treated daily with bromocriptlne (Sandoz CB‐154, an inhibitor of PRL release) or with vehicle. After three weeks, the weights of the testes and the seminal vesicles were significantly lower in bromocriptine‐treated than in control hamsters, but after five and a half weeks these differences were no longer evident.

We conclude that (1) suppression of the release of both PRL and gonadotropins is responsible for gonadal regression in short photoperiod, and (2) stimulation of PRL secretion contributes to recrudescence of the male reproductive system in long photoperiod.
Effect of Anesthetics on Testosterone Production in Rats
Authors: FREE MICHAEL J. , JAFFE RICHARD A. , CHENG HSIEN‐CHEN
Published: December 2015

Changes in testicular vein and peripheral testosterone concentrations in mature rats were monitored during anesthesia with six different agents. Samples taken 2–3 minutes after initial disturbance of the resting animal yielded mean testicular vein testosterone levels of 59–247 ng/ml plasma in nine separate groups of rats. Sustained anesthesia under halothane, enflurane, pentobarbital, ether, urethan, or ketamine/promazine resulted in a decline in testicular vein testosterone to 10–60 ng/ml by the third hour. Luteinizing hormone levels, measured under enflurane anesthesia, also fell significantly by 1 and 2 hours after administration of anesthesia, although follicle‐stimulating hormone remained constant. Testes of the enflurane‐anesthetized rat were still able to respond to gonadotropins, but withdrawal of the anesthetic did not reverse the downward trend in testosterone. No changes in testicular blood flow were detected during anesthesia, although flow under urethan anesthesia was consistently slower than with other agents. The first 90 minutes of urethan anesthesia were characterized by severe fluctuations in testicular vein testosterone. Halothane, enflurane, and pentobarbital resulted in a larger ratio of peripheral to testicular vein testosterone compared with ether or rapid sampling, suggesting a reduction in turnover rate under these three agents. Conclusions were that different anesthetic agents can distort hormone levels and endocrine function of the testes in various ways, and that the production rate of testosterone by rat testes is higher than has been previously suggested.
Testosterone Regulation of Follicle‐stimulating Hormone Secretion in the Male Dog
Authors: FALVO RICHARD E. , VINCENT DOUGLAS L.
Published: December 2015

Studies were carried put to determine the effect of various numbers of testosterone‐filied polydimethylsiloxane (PDS) capsules on plasma concentrations of testosterone and FSH in acutely orchidectomized dogs. Dogs were implanted with either one empty PDS capsule or one, three, or five testosterone‐filled PDS capsules. Blood samples were collected daily prior to implantation, following implantation, following castration, with capsules left in situ, and following capsule removal. Replacement of testosterone, using one testosterone‐filled capsule, did not prevent the postcastration rise of FSH. Replacement of testosterone, using three and five testosterone‐filled capsules, maintained both FSH and testosterone in castrated dogs at concentrations similar to those observed in intact animals. Removal of testosterone‐filled capsules from castrated dogs resulted in hypersecretion of FSH. These studies indicate that testosterone replacement within physiologic limits will maintain FSH in the acutely orchidectomized dogs at concentrations similar to those observed in intact, untreated animals.
Antifertility Effects of LHRH Agonists in the Male
Authors: LABRIE FERNAND , BÉLANGER ALAIN , CUSAN LIONEL , SEGUIN CARL , PELLETIER GEORGES , KELLY PAUL A. , REEVES JERRY J. , LEFEBVRE FLEUR‐ANGE , LEMAY ANDRE , GOURDEAU YVES , RAYNAUD JEAN‐PIERRE
Published: December 2015

Acute or chronic treatment of adult male rats with LHRH or its agonists leads to a loss of testicular LH and prolactin receptors accompanied by decreased testis, seminal vesicle, and ventral prostate weight. The inhibition of testosterone formation is due to a blockage of the steroidogenic pathway at the level of 17‐hydroxylase and 17,20‐desmolase activities. The testicular desensitization is accompanied by a decreased pituitary responsiveness to LHRH. Although the inhibitory effects at the testicular level could be explained by endogenous LH release induced by the LHRH agonist with secondary testicular desensitization, the LH‐releasing peptides also exert direct inhibitory effects on gonadotropin receptors at the testicular level. Moreover, LHRH and its agonists bind to a specific LHRH receptor in interstitial cells. Chronic treatment with LHRH agonists leads to marked degenerative changes in the seminiferous tubules, almost all tubules showing signs of histologic damage after four weeks of treatment. Single administration of an LHRH agonist by the intranasal route in normal adult men causes a transient inhibition of plasma testosterone levels with a temporary loss of diurnal cyclicity, whereas preliminary data obtained in patients with cancer of the prostate show inhibition of both testosterone and dihydrotestosterone plasma levels. Such data suggest the potential use of LHRH agonists in male contraception and for the treatment of cancer of the prostate.
Androgen and Estrogen Receptors in the Canine Prostate
Authors: HAWKINS EDWARD F. , TRACHTENBERG JOHN , HICKS L. LOUISE , WALSH PATRICK C.
Published: December 2015

Characterization of cytosol and 0.6 M KCl‐nuclear androgen and estrogen receptors in the canine prostate is described, including methods for assay of these molecules in tissue samples from intact, adult dogs. Androgen receptors were quantitated by exchange incubations (20 hours for cytosol and 26 hours for nuclear extract at 0 C; incubations at higher temperatures (15 or 30 C) resulted in substantial reduction of saturable binding activity. Apparently, virtually all the estrogen receptor sites in cytosol and nuclear extract are unoccupied, since these were equally filled with H3‐estradiol at 0 C (nonexchange incubation) and 30 C (exchange conditions) during 20‐hour incubations. Androgen receptors were assayed using the synthetic androgen methyltrienolone (R1881), and estradiol‐17β was selected for estrogen receptor determinations. Using the assay conditions described, neither of these ligands bound to the sex steroid‐binding protein of canine blood. Steroid competition experiments indicated that the androgen and estrogen receptors are distinct molecules. Scatchard plot analyses were linear, suggesting a single class of high affinity sites for each receptor (Kd's in the 10−9 to 10−10 mol/l range). Saturable estradiol binding was additionally detected by sucrose gradient analysis of cytosol and nuclear extract. The 4S sedimentation of the cytosol receptor is typical of prostate cytoplasmic estrogen receptors; the nuclear form sedimented at 5S. The estrogen and androgen binding proteins satisfy criteria that distinguish them from blood steroid binding proteins and classify them as intracellular steroid hormone receptors.
The Suitability of Silver and Platinum Coils as Intravasal Devices for Male Fertility Control in Rats
Authors: ROVAN E. , AULITZKY H. , FRICK J. , STEINER M. , KOEHLE R. , WEISKE W.
Published: December 2015

In 91 male rats, silver or platinum coils were Implanted into the vasa deferentia with the hope of developing a simple and reversible method for male fertility control. The insertion of the coil by inguinal incision promises a high success rate, and side effects such as sperm granuloma, device extravasation, displacement of the testes, and artificial ascensus could be prevented. In an in vitro experiment simulating the vas deferens anatomical conditions, the immobilizing capacity of the device was evident, and the motility of the spermatozoa decreased to 0% within 30 minutes. Longterm in vivo experiments showed no changes in the reproductive organs. However, the high rate of pregnancy after placement of the device (55%) does not suggest that such devices could offer a practical method of achieving male sterility.
Effect of Vasectomy on the Retinal Vasculature of Men
Authors: FAHRENBACH HILDEGARD B. , ALEXANDER NANCY J. , SENNER JOHN W. , FULGHAM DAVID L. , COON LYNN J.
Published: December 2015

Ophthalmoscopic examination of the retinal vasculature of 159 men over age 30 showed a significant increase in mild vascular changes in vasectomized as compared to nonvasectomized men. Although this preliminary study revealed no significant difference in blood pressures when the two groups were compared, vasectomized men age 40 and under had an increased frequency of arteriolar constriction in comparison with the control group. The authors suggest that this noninvasive method may be useful for future studies.
Effects of Chronic, High‐dose LHRH‐Agonist Treatment on Pituitary and Testicular Functions in Rhesus Monkeys
Authors: WICKINGS E. JEAN , ZAIDI PERVEEN , NIESCHLAG EBERHARD
Published: December 2015

The effects of chronic, high‐dose treatment with an LHRH‐agonist (D‐Ser‐(TBu)6‐LHRH‐ethylamide) on pituitary and testicular functions were investigated in four adult rhesus monkeys In‐season. Doses of 4 μg of agonist per day for eight weeks followed by 20 μg/day for four weeks caused a significant decrease in testicular volume and a transient suppression of sperm counts, although counts at the end of treatment were not different from control values. Basal levels of LH were not altered by chronic treatment. Responses to acute stimulation with high and low doses of LHRH or the agonist were measured in terms of the LH increase over basal values and the cumulative response. The results indicate that the pituitary capacity was not affected, but that the sensitivity to low doses was decreased after 12 weeks. Basal testosterone concentrations were decreased during the early and later phases of treatment. The testosterone increase In response to acute stimulation with LHRH or its agonist was not suppressed by chronic treatment, although the cumulative response to low doses of both substances was less after 12 weeks of treatment with high doses of the agonist.
Relationship of Spermatozoal Migration in Cervical Mucus to Bovine Fertility
Authors: KUMMERFELD HANS L. , LORTON STEVEN P. , FOOTE R. H.
Published: December 2015

Frozen bovine semen from males of wellestablished, generally high fertility levels was thawed and used in three experiments for In vitro capillary tube migration through cervical mucus. Bovine cervical mucus from individual heifers or a group of heifers was evaluated in these assays. Correlations between spermatozoal migration and bull fertility were small and not significant. Significant differences in spermatozoal migration distances were due to bulls, source of mucus, and storage time of mucus before use in the assay. These differences did not appear to affect the correlations obtained, but they require that the sperm migration test be standardized relative to sources of mucus and storage time if different seminal specimens are to be compared.
Virilizing Testicular Tumor: In Vivo Studies of Steroid Secretion
Authors: PENNY ROBERT , STANCZYK FRANK Z. , TURKEL SUSAN B. , ISERI ALLEN L. , GOEBELSMANN UWE T. , FRASIER S. DOUGLAS
Published: December 2015

Findings in a six‐year‐old boy with a virilizing tumor of the left testis are presented. His bone age was 14 years. Serum testosterone (5.9 nglml), urinary 17‐ketosteroid (29 mg/24 hr), and pregnanetriol (14 mg/24 hr) excretion was elevated. These values were not suppressed after the administration of dexamethasone. Spermatic‐peripheral vein concentration differences showed that the tumor secreted 17‐hydroxy‐pregnenolone, dehydroeplandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA‐S), progesterone, 17‐hydroxyprogesterone, androstenedione, testosterone, estrone, estradiol, 11‐desoxycortisol, and corticosterone. The tumor did not secrete cortisol. Electron microscopy study of the tumor revealed a dimorphic population of light and dark cells with many features seen in Leydig cell tumors. However, these were not distinct from those of adrenal rest tumors. Reinke crystalloids were not found. True precocious puberty developed five months after tumor removal, ie, the right testis increased in size, and serum gonadotropins increased. Seven months after tumor removal, the patient was demonstrated not to have impaired cortisol synthesis, ie, urinary 17‐hydroxysteroids increased from 1.8 to 38.0 mg/24 hr In response to adrenocorticotropic hormone (ACTH) administration. The differential diagnosis of virilizing testicular tumors lies between Leydig cell adenoma and adrenal rest tumor in California congenital adrenal hyperplasla. The demonstration that the patient did not have Impaired cortisol synthesis is consistent with his tumor being a Leydig cell adenoma.
Disappearance of Inhibin‐like Activity in Bull Seminal Plasma Following Castration
Authors: SAIRAM M. R. , RANGANATHAN M. R. , RAMASHARMA K. , LAMOTHE P.
Published: December 2015

Ejaculates from normal and castrated bulls were evaluated for the presence of inhibin‐like activity. Inhibin activity found in the seminal plasma of normal bulls became undetectable after castration. Crude protein concentrates prepared from the ejaculates of castrated bulls failed to produce inhibition of FSH secretion as measured by in vivo and in vitro tests: a) hCG‐induced uterine weight test in mice and b) LH‐RH‐induced FSH secretion in 34‐day‐old male mouse pituitary. The concentrates also lacked the ability to inhibit the binding of iodine‐125 (125I)‐labeled inhibin fraction from normal bull seminal plasma to ovine pituitary membranes. Chromatographic and electrophoretic analyses of the ejaculate from castrated bulls revealed the absence of the band corresponding to inhibin of normal bull seminal plasma.
Electrophoretic and Chromatographic Properties of Boar Sperm Plasma Membranes: Antigens and Polypeptides with Affinity for Isolated Zonae Pellucidae
Authors: PETERSON R. N. , RUSSELL L.D. , SPAULDING G. , BUNDMAN D. , BUCHANAN J. , FREUND M.
Published: December 2015

Two methods were used to assess the ability of plasma membrane (PM) polypeptides to bind to isolated zonae pellucidae (ZP). Crossed immunoelectrophoresis patterns of detergent solubilized PM were compared in the presence and absence of ZP. Two antigens which represented less than 20% of the total antigen response were significantly changed in electrophoretic mobility and precipitin peak height. In the second experiment, detergent solubilized PMS, labeled with iodine‐125 (1125), were absorbed to a column containing purified ZP. Washed columns eluted with SDS‐urea were found to be enriched in several polypeptides which migrate in PAGE‐SDS gels below 22 Kd. Comparison of PAGE patterns of PM originating primarily from the sperm head with those enriched in PM from other regions of the sperm surface suggest that these low molecular weight polypeptides with affinity for isolated ZP are concentrated in the sperm head. These experiments provide a base for determining which PM components are involved in spermegg interactions in vivo.
Pituitary—Testis Relationships in Paraplegic Men
Authors: CORTÉS‐GALLEGOS VICENTE , CASTAÑEDA GRACIELA , ALONSO ROCÍO , ARELLANO HORTENSIA , CERVANTES CARLOS , PARRA ADALBERTO
Published: December 2015

Ten men aged 12 to 48 years with a complete neurophysiologic transection of the spinal cord (seven paraplegic, two quadriplegic, and one hemiplegic) were endocrinologically investigated to determine the relationships between the plasma concentrations of gonadotropins, prolactin, and androgens and to search for possible correlations with the time elapsed after the trauma (one‐79 months). Peripheral blood samples were obtained from each subject every other day to measure follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), androstenedione (A), testosterone (1), and dihydrotestosterone (DHT), and the results were compared with the values obtained from age‐matched healthy individuals. On a group basis (without including two prepubertal patients), a significant linear correlation was observed between the time elapsed after the trauma and the plasma levels of T (r= 0.683,P= 0.05) and DHT (r= 0.832,P< 0.025), but not A. Both FSH and LH plasma concentrations were elevated in all instances, and 70% of the patients also had higher PRL values when compared with healthy male subjects. The present study emphasizes the need for a careful re‐examination of the current clinical management of these patients within the first months after trauma.
Inhibition of Spermatogenesis and Steroidogenesis During Long‐Term Treatment with hCG in the Rat
Authors: CUSAN L. , PELLETIER G. , BÉLANGER A. , SÉGUIN C. , KELLY P. A. , LABRIE F.
Published: December 2015

The effects of chronic treatment with hCG (100 I.U. s.c. every second day) on testicular morphology, LH receptor levels and concentration of steroid intermediates of the δ4 and δ5 biosynthetic pathways were studied in adult rats for periods extending from one to 12 weeks. Treatment with hCG causes a decrease in testis weight, a maximal inhibitory effect being observed after two and four weeks of treatment. At these time intervals, the loss of testis weight is accompanied by degenerative changes in most seminiferous tubules and hypertrophy of Leydig cells. Administration of hCG for one week leads also to an almost complete loss of LH binding sites and to a marked stimulation of the levels of testicular steroids of the A and pathways, as well as to an increase in weights of secondary reproductive organs. The initial increment of testicular steroid levels is followed after two weeks of hCG administration by an apparent decrease of 17, 20‐desmolase activity suggested by a reduction in the levels of androst‐5‐ene‐3β, 17β‐diol, androstenedione, testosterone, and 5α‐dihydrotestosterone and an increase in the concentrations of pregnenolone, 17‐OH‐pregnenolone, progesterone and 17‐OH‐progesterone. Plasma and pituitary LH levels are maximally reduced at one and four weeks of treatment, respectively, while plasma and pituitary FSH levels are only slightly reduced after four weeks of hCG administration. The effects of hCG on all of the above‐mentioned parameters, except for testicular morphology and testis weight, are completely reversible at the eight and 12 week intervals. This transiency in the effects of hCG is accompanied by a gradual increase in plasma levels of hCG antibodies. The present data show that chronic treatment of adult rats with hCG induces a marked degeneration of the seminiferous tubules and an inhibition of spermatogenesis that accompanies the well‐known loss of testicular LH receptors and inhibition of the steroidogenic pathway.
The Effects of Cyclic Adenine Nucleotides, Phosphodiesterase Inhibitors, and Cauda Epididymidal Fluid on the Motility of Rat Epididymal Spermatozoa
Authors: TURNER T. T. , GILES R. D.
Published: December 2015

Experiments were performed to determine whether the rat epididymis secretes a “forward‐motility” factor(s) similar to that found by others in the bovine epididymis. Lumen content of the rat caput and cauda epididymidis was collected by micropuncture. Caput and cauda spermatozoa were diluted in.154 M NaCl, 25 mM theophylline, or 10 mM cAMP, dibutyryl cAMP, 8‐bromo cAMP, or 8‐bromo AMP in saline. Progressive motility was judged by determining linear distance traveled by sperm in the various diluents after 30‐minute incubation at 37 C. Neither theophylline nor cyclic adenine nucleotides cause caput sperm to swim distances attained by cauda spermatozoa. In other experiments, caput spermatozoa were preincubated for either 5 or 30 minutes at either 32 C or 37 C with fresh cauda lumen fluid prior to dilution with the test solutions. Cauda fluid did not significantly enhance the progressive motility of caput sperm in any diluent. Stimulation with 25 mss theophylline always resulted in more distance traveled than with any other diluent. This effect was reproduced by 25 mM caffeine, another xanthine phosphodiesterase inhibitor (PDI). There was no stimulation of motility with 200 LM papaverine, a nonxanthine PDI. The results of this study failed to demonstrate the presence of a factor in lumen fluid of the distal rat epididymis that acts in conjunction with cyclic adenine nucleotides to induce mature cell motility in immature spermatozoa.
A Method for the Determination of Chlorinated Pesticides in Human Semen
Authors: SZYMCZYNSKI GRZEGORZ A. , WALISZEWSKI STEFAN M.
Published: December 2015

A method is described for the quantitative and qualitative determination of BHC and DDT isomers and HCB and Methoxychlor (DMDT) in human semen. Pesticide residues were extracted with petroleum ether, separated from other co‐extractives on Florisil column, and analyzed by electron‐capture gas chromatography. Recoveries were 96.4 to 110.8% and fortification levels were 0.02 to 0.20 μg/g, respectively.
Relationship of Human Sperm Acrosin and Proacrosin to Semen Parameters. I. Comparisons Between Symptomatic Men of Infertile Couples and Asymptomatic Men, and Between Different Split Ejaculate Fractions
Authors: GOODPASTURE JESSIE C. , ZAVOS PANAYIOTIS. , COHEN MELVIN R. , ZANEVELD LOURENS J. D.
Published: December 2015

Acrosin is a sperm serine proteinase whose activity appears to be essential for fertilization in mammals, although this has not been shown in man due to experimental limitations. The present study shows that the concentrations of acrosin and its precursor, proacrosin, are significantly higher (P <0.001) in the spermatozoa of asymptomatic men (those having no seminal abnormalities or known fertility impairments) than of symptomatic men (those from infertile couples showing at least one abnormal seminal parameter). It is demonstrated additionally that the spermatozoa of the first fraction of split ejaculates contain significantly greater quantities of acrosin and proacrosin when compared to the spermatozoa from the second fraction of the same split ejaculates (P <0.001). The fertility potential of the first fraction is generally accepted to be greater than that of the second fraction. These data, together with our earlier findings on the acrosin and proacrosin content of fresh and cryopreserved human spermatozoa (Goodpasture et al, 1981), suggest that subfertility or infertility in man may be related to a low acrosini proacrosin content of spermatozoa.
The Effects of Experimental Cryptorchidism on the Entry of [3H]‐Inulin and [3H]‐Horseradish Peroxidase into the Lumen of the Rat Seminiferous Tubules
Authors: TURNER T. T. , D'ADDARIO D. A. , FORREST J. B. , HOWARDS S. S.
Published: December 2015

The objective of this research was to determine if experimental cryptorchidism causes significant changes in the rat blood‐testis barrier. Micropuncture of the seminiferous tubules of normal, sham‐operated, or surgicaily‐cryptorchid rats was performed after intravenous infusion of [3H]‐inulin or subtunica injection of [3H]‐horseradish peroxidase. Concentration of the isotopes in the lumen of the seminiferous tubule was determined. Normal, sham, and cryptorchid tissues were also immersed in hypertonic (.75 M) LiCI and prepared for observation by light microscopy.

Micropuncture experiments demonstrated that cryptorchidism significantly increased the penetration of the blood testis barrier by [3H]‐inulin and [3H]‐horseradish peroxidase. The LiCI emersion techniques, a histological method of visually detecting the presence of an intact blood‐testis barrier, also demonstrated partial disruption of the blood‐testis barrier in the cryptorchid testis. In spite of these alterations, the seminiferous tubules of the experimentally‐cryptorchid testes retained a large proportion of their capacity to exclude macromolecules.
Endogenous Steroids in the Rat Seminiferous Tubules. Comparison of the Stages of the Epithelial Cycle Isolated by Transillumination‐Assisted Microdissection
Authors: PARVINEN MARUI , RUOKONEN AIMO
Published: December 2015

A microdissection procedure is described that allows the isolation of segments of rat seminiferous tubules in different stages of the epithelial cycle. This procedure is based on spermatogenic stage‐dependent differences in the transillumination pattern along the freshly isolated, unstained seminiferous tubules. It allows collection of segments representing defined stages in amounts sufficient for biochemical studies (5–10 mg wet weight).

Tubular segments at stages I, II–III, IV–V, VI, VIIa–b, VIIc–d, VIII, IX–XI, XII, and XIII–XIV have been used for measurement of endogenous concentrations of testosterone, 5α‐dihydrotestosterone, progesterone, and 17α‐hydroxyprogesterone by radioimmunoassays after Lipidex‐5000 chromatography. Testosterone was the most abundant steroid at all stages of the cycle, and its concentration at stage VIII was significantly higher than at any other stage. The concentration of 5α‐dihydrotestosterone was markedly lower and did not exhibit similar differences in distribution. The levels of progesterone and 17α‐hydroxyprogesterone were the same at all stages of the cycle of the seminiferous epithelium.

A number of morphologic and biochemical observations suggest unique changes in the metabolic activity of both germ cells and Sertoli cells at stages VII and VIII of the cycle. The possible androgen control of these changes is discussed.
Catecholamine Stimulation of Androgen Production by Mouse Interstitial Cells in Primary Culture
Authors: MOGER WILLIAM H. , MURPHY PAUL R. , CASPER ROBERT F.
Published: December 2015

The catecholamines isoproterenol, epinephrine, and norepinephrine stimulated androgen production by mouse interstitial cells in primary culture. The amount of androgen produced in response to maximum stimulation with these amines was less than that produced with maximum human chorionic gonadotropin stimulation, but produced an additive effect when combined with a submaximal concentration of human chorionic gonadotropin. The stimulatory effect of isoproterenol could be blocked by the β‐receptor antagonist propranolol. Isoproterenol did not stimulate androgen production by either freshly isolated mouse interstitial cells or whole decapsulated testes.
The Relationships Between Serum Testosterone and Prolactin Levels and Nocturnal Penile Tumescence (NPT) in Impotent Men
Authors: CUNNINGHAM GLENN R. , KARACAN ISMET , WARE J. CATESBY , LANTZ GORDON D. , THORNBY JOHN I.
Published: December 2015

Serum testosterone (T) and prolactin (PRL) levels, nocturnal penile tumescence (NPT), penile and brachial blood pressure, and bulbocavernosus reflex latency (BCR) were assessed in 172 impotent men ranging in age between 19 and 60 years. Patients were also examined for Peyronie's disease. Patients who were taking drugs that are known to affect T or PRL levels, and those with overt primary or secondary testicular failure, liver disease or renal disease, were excluded from the study.

Androgen deficiency (T <264 ng/dl) or hyperprolactinemia (PRL > 15 ng/ml) was observed in 22% of the patients, and 62% had abnormal NPT. We found that NPT was abnormal in 11 of the 12 men (91.7%) with T levels below 251 ng/dl or with PRL levels above 25 ng/ml (P <.001), and in 81.0% to 93.8% of men with other detectable and relevant medical abnormalities. Eight of the 12 patients with T levels below 251 ng/dl or PRL levels above 25 ng/ml had other detectable abnormalities. In contrast, NPT was abnormal in only 10 of 34 men (29.4%) who had no apparent medical abnormality or disease.

These studies indicate that in impotent men, T deficiency and/or hyperprolactinemia, alone or with other conditions, are associated with abnormal NPT sufficiently frequently to warrant routine measurement of both T and PRL, particularly if it can be demonstrated that correction of these abnormalities restores potency.
The Regulation of Gonadotrophin Secretion in Immature Ethanol‐Treated Male Rats
Authors: RAMALEY JUDITH A.
Published: December 2015

Exposure of immature male rats to 5% (w/v) ethanol as the sole drinking fluid from weaning age (21 days of age) resulted in a delay in balanopreputial separation (41.3 ± 1.4 days versus 37.6 ± 2.0 days in controls reared on tap water, P <0.02). The purpose of this study was to determine whether this delay was associated with changes in the regulation of gonadotrophins in the prepubertal period. Three tests of gonadotrophin response were used: 1) the measurement of FSH and LH levels during the first 48 hours after castration performed at 28 days of age; 2) the sensitivity of the castration response to replacement therapy with testosterone propionate (TP) or estradiol benzoate (EB); and 3) the response of 25, 28, or 32‐day‐old males to doses of GnRH ranging from 2 to 200 ng/100 g body weight. Basal FSH levels were elevated in ethanol‐treated rats but LH values were normal. Both FSH and LH concentrations rose more rapidly in the first 48 hours after castration in 28‐day‐old ethanol‐treated animals than in controls. When replacement therapy with TP was initiated just prior to castration, ethanol‐treated rats were slightly less sensitive to the suppressive effects of TP as indicated by the rate of rise of both FSH and LH levels during the first 48 hours after surgery. Castrated ethanol‐treated rats were also slightly hess sensitive to the suppressive effect of 0.5 μg estradiol benzoate (EB). The ability of EB to suppress basal levels of LH in intact males at 28 days of age was similar in the two groups, but a significant decrease in FSH levels occurred in intact ethanol‐treated rats. The pituitary response to GnRH decreased in both control and ethanol‐treated rats from 25 to 32 days of age. At all ages tested, the FSH response was less in ethanol‐treated animals than in controls. The LH response was lower in 25 and 32‐day‐old ethanol‐treated rats than in controls. There was no difference between the LH responses in the control and the experimental groups at 28 days of age. It is concluded that the pubertal delay initiated by ethanol is associated with abnormalities in gonadotrophin, and especially FSH, regulation during the prepubertal period in the male rat.
Control of Rat Testicular Prostaglandin Dehydrogenase, δ13‐Prostaglandin Reductase, and Total Prostaglandin Hypophysectomy, Follicle Stimulating Hormone, Luteinizing Hormone, Prolactin, Growth Hormone, and Testosterone
Authors: OHUO‐OBASIOLU CHARLES C. , GROESBECK MICHAEL D. , ELLIS LEGRAND C.
Published: December 2015

The effects of hypophysectomy and various hormonal treatments on rat testicular prostaglandin dehydrogenase (PGDH), δ13‐PG reductase, and total PGDH activities were studied in vivo and in vitro. All three activities were reduced, on a per animal basis, by hypophysectomy. Treatment with FSH increased all three activities while prolactin or GH plus LH inhibited only Δ13‐PG reductase activity, the inhibition being evident both in vivo and in vitro. Prolactin ameliorated the effects of FSH in vivo and the gonadotropin effects were considered to be allosteric in nature. The highest specific activity for total PGDH activity was found in the testicular capsule followed by the interstitial cells and the seminiferous tubules. The seminiferous tubules had more total activity than did the interstitial cells and testicular capsule. PGDH activities in the three structural compartments of the testis were considered physiologically related to the functions of these compartments, ie contractility or steroidogenesis. Changes in the specific activity of PGDH indicated that the enzymes in the seminiferous tubules were localized within nongerminal cells.
Transformations of Sperm Nuclei Incorporated Into Aged and Unaged Hamster Eggs
Authors: LONGO FRANK J. , SO FREDERICK
Published: December 2015

The extent of male pronuclear development in aged and unaged hamster eggs was examined by electron microscopy. Observations are presented demonstrating that although hamster eggs, aged 18 hours in vivo and lacking zonae pellucidae, may be fertilized in vitro, transformation of incorporated sperm nuclei into male pronuclei is significantly retarded. By 6 hours postinsemination, 50% of the sperm nuclei incorporated into aged eggs failed to disperse (vs. 19% in unaged eggs); sperm were observed in various stages of dispersion (20%), but only 30% developed into pronuclei (vs. 18 and 63% in unaged eggs, respectively). These results are discussed in reference to concepts of nucleocytoplasmic interactions involving male pronuclear development.
Leydig Cell Function in Long‐term Testosterone‐immunized Rats
Authors: SHARPE RICHARD M. , FRASER HAMISH M.
Published: December 2015

To assess the role of androgen feedback in the regulation of the Leydig cell, adult rats were actively immunized against testosterone (T) for a period of 12 months, and Leydig cell function then assessed. In T‐immunized rats, the number of LH receptors per Leydig cell and the capacity of these cells to secrete testosterone in vitro were increased 3‐fold, while there was a smaller increase in the number of LHRH receptors per cell. These changes were associated with increases in serum levels of LH, FSH, and testosterone of approximately 8‐fold, 2.5‐fold, and 50‐fold, respectively. To test whether increased exposure to LH was responsible for the observed stimulation of Leydig cell function, the effect of a single injection of hCG was assessed. However, this treatment inhibited Leydig cell function, causing a similar loss in the percentage of LH and LHRH receptors in control and T‐immunized rats. While hCG injection reduced T responsiveness of Leydig cells from T‐immunized rats, surprisingly, it had the opposite effect in controls; the latter effect was probably a consequence of the age of the animals involved. These findings show that interference with androgen feedback results in stimulation of certain parameters of Leydig cell function. However, the observed changes cannot be explained simply by increased exposure to LH, suggesting that other factors, such as intratesticular androgen feedback mechanisms, are involved.