bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Intracoronary Lidocaine on Ventricular Arrhythmia in the Infarcted Canine Heart
Authors: Tordjman Therese , Raeder Ernst , Lampert Steven , Lown Bernard
Published: December 2015

The efficacy of intracoronary administration of lidocaine was studied in three groups of dogs with experimental myocardial infarction induced by occlusion of the left anterior descending coronary artery (LAD). Group 1 included 14 anesthetized and group 2, 7 conscious animals to which lidocaine 1.4 μg/kg/minute was administered as an intracoronary infusion. Group 3 consisted of 17 anesthetized dogs that received an intracoronary bolus of lidocaine 40 μg/kg over 30 seconds. In group 1, lidocaine reduced ventricular arrhythmia by 59±30% (p 0.001), whereas systemic lidocaine achieved a reduction by 61±37% (p 0.06). In seven dogs, lidocaine blood levels were measured in the great cardiac and femoral veins. At the end of the infusion the drug concentration was 3.4 ± 2.2 μg/ml in the great cardiac and 1.3±1.1 μg/ml in the femoral vein (p<0.05). The reduction in ventricular arrhythmia correlated with the great cardiac vein lidocaine concentration (r = 0.70; p<0.05), but not with the drug level in the femoral vein (r = 0.06; NS). In group 2, lidocaine was ineffective by both routes of administration. This may have been related to higher sympathetic activity, as suggested by an elevated heart rate in conscious compared to anesthetized animals (186 ±6 vs 164 ± 21 bpm; p 0.0054). In group 3, bolus injections of lidocaine into the LAD reduced ventricular arrhythmia by 66% (p 0.001). We conclude that by perfusing the infarcted zone with lidocaine, a significant antiarrhythmic effect can be achieved with 2% of the systemic dose. This approach may permit abbreviated antiarrhythmic drug testing while avoiding the extracardiac side effects frequently observed with these agents.
The Positive Association of Cough with Angiotensin‐Converting Enzyme Inhibitors
Authors: Just Paul M.
Published: December 2015

Captopril, enalapril, lisinopril, ramipril, cilazipril, and quinipril have all been documented to induce cough with an estimated frequency of at least 15% of treated patients. Common descriptors include tickling, dry, nonproductive, and persistent. Onset usually occurs during the first week of therapy and lasts as long as the drug is taken, remitting within a few days after the agent is discontinued. Alternative angiogensin‐converting enzyme (ACE) inhibitors replicate the cough. The mechanism seems related to stimulation of lung afferent C fibers, perhaps by prostaglandin E2. It may also be related to decreased breakdown of substance P, the neurochemical mediator of the cough reflex released in response to stimulation of C fibers and metabolized by ACE. The possible role of prostaglandins is supported by two anecdotal reports of cough disappearing in patients receiving nonsteroidal antiinflammatory agents. Future trials should recognize cough as a side effect of ACE inhibitor therapy, and prospective determination of its true frequency and cross‐occurrence are necessary.
On the Fringes
Authors: Green Jeffrey A. , Munger Mark A.
Published: December 2015

The expanded training pharmacists now receive in human pharmacotherapy has led to their increased participation in direct patient care. These activities may be global or specific, and can include drug therapy consultation, pharmacokinetic‐based dosing recommendations, drug‐use review, participation in nutritional support, and clinical pharmacology research. Such a listing of relatively sophisticated roles makes today's pharmacy practitioners almost unidentifiable with their counterparts of 20 years ago. This rapid transition makes pharmacy somewhat different in the health professions, since in comparison, medicine and nursing have been more stable. Despite these hard‐fought advancements, there is a disturbing discrepancy between standards of care in pharmacy and the legal definition of pharmacy practice. Continued and future advancements are tenuous secondary to fear generated from noncompliance with state regulations. The entire profession should strive to develop updated pharmacy acts to prevent individuals from practicing “on the fringes.”
Comparison of Disposition Values Obtained by Two Assay Methods for Quinidine Gluconate in Patients with Ventricular Tachycardia
Authors: Ackerman Bruce H. , Olsen Keith M. , Kennedy Eleanor E. , Taylor E. Howard , Chen Bai H. , Jordan Drexel , Ackerman Deborah J.
Published: December 2015

Eight patients with previously untreated ventricular tachycardia, age 48.54 ± 28.02 years (mean ± SD), were enrolled in a protocol evaluating the disposition of quinidine gluconate as determined by two assay methods. Patients received two infusions of 5 mg/kg over 30 minutes separated by 20–30 (24.9 ± 4.0) minutes of electrophysiologic testing. Blood samples were obtained at 0.17 hours and just prior to the second infusion, and then at 0.17, 0.25, 0.33, 1.0, 6.0, 12.0, and 24.0 hours after the second infusion. Paired serum samples were assayed for quinidine concentrations by fluorescence polarization immunoassay and high‐performance liquid chromatography. The two assays compared well, with a linear regression equation of Y = 0.927X + 0.247 with a correlation coefficient of 0.985. With the exception of the ß elimination rate constant and ß distribution volume, t test comparison of disposition values demonstrated no significant difference. Differences in the estimates of the ß elimination rate constant reflected differences in the two methods and indicated that even though both assays were comparable, subtle differences in specificity could be reflected in significant differences in this variable.
Dobutamine: Ten Years Later
Authors: Majerus Thomas C. , Dasta Joseph F. , Bauman Jerry L. , Danziger Larry H. , Ruffolo Robert R.
Published: December 2015

Dobutamine is a commonly used positive inotrope for the short‐term management of heart failure. It is commercially available as a 50:50 mixture of two isomers with unique effects on α‐ and β adrenergic receptors. In dosages of 2–15 μg/kg/minute, dobutamine has been shown to increase cardiac output (mainly through stroke volume), reduce systemic vascular resistance, lower central venous and pulmonary artery wedge pressures, improve renal blood flow, and relieve signs and symptoms of congestive heart failure. At higher dosages it can increase heart rate and induce arrhythmias. Recent evidence indicates that effects of dobutamine last long after the drug has been eliminated from the plasma, and some work has been done on ambulatory use of this agent. Dobutamine has been used successfully in several circumstances, such as after cardiac surgery, in patients with myocardial infarction, and in various shock states. An understanding of the pathophysiology of the underlying disorder is important in deciding which catecholamine to use. With this in mind, monotherapy or combination therapy with inodilators such as dobutamine, or inopressors like dopamine will follow logically.
Meta‐Analysis: Whither Narrative Review?
Authors: Teagarden J. Russell
Published: December 2015

Meta‐analysis refers to methodologies that are used to integrate related empirical research to arrive at conclusions not possible by reviewing individual studies, or to improve generalizations of individual studies. It is distinguished from the traditional narrative review in that statistical methodologies are applied to derive more objective conclusions than those that typify narrative reviews. Meta‐analysis has been slow to appear in the literature of clinical medicine, however, particularly when viewed in the context of the exponential expansion of literature and the availability of computer technology to facilitiate its conduct.
Hemodialysis Removal of Propafenone
Authors: Burgess Ellen D. , Duff Henry J.
Published: December 2015

Propafenone kinetics were studied after intravenous and oral dosing in a patient with end‐stage renal disease. Hemodialysis was performed within 10 hours of dosing in order to assess its effects. After intravenous administration of 70 mg propafenone, total‐body clearance was 10.5 ml/min/kg before and 10.4 ml/min/kg during hemodialysis. After a single oral dose of 300 mg, clearance was 19.4 ml/min/kg before and 18.9 ml/min/kg during hemodialysis. Bioavailability was 48%.
Glycosaminoglycan Stimulation of the In Vitro Conversion of Boar Proacrosin into Acrosin
Authors: PARRISH RICHARD F. , WINCEK THOMAS J. , POLAKOSKI KENNETH L.
Published: December 2015

Glycosaminoglycans obtained from shark cartilage, whale cartilage, porcine intestinal mucosa, porcine skin, and human umbilical cord were found to accelerate the in vitro conversion of highly purified boar sperm proacrosin Into mα‐acrosin. Since none of the glycosaminoglycan preparations demonstrated esterase activity (BzArgOEt), general proteinase activity (Azocoll), or stimulation of acrosin activity, the glycosaminoglycan stimulation of proacrosin conversion into acrosin results from a direct Interaction between proacrosin and the glycosaminoglycans. These results demonstrate that the glycosaminoglycan stimulation of proacrosin conversion into acrosin is a general phenomenon that is not speciesor organspecific and indicate that glycosaminoglycans could function in the regulation of the In vivo conversion of proacrosin into acrosin.
A Possible Relation between Elevated FSH Levels and Leydig Cell Dysfunction in Azoospermic and Oligospermic Men
Authors: RODRIGUEZ‐RIGAU LUIS J. , SMITH KEITH D. , STEINBERGER EMIL
Published: December 2015

Plasma testosterone, follicle‐stimulating hormone (FSH), and luteinizing hormone (LH) levels were measured in the male partners of 69 infertile couples and in 260 allegedly fertile men requesting vasectomy. All hormone levels were within normal range in men with total sperm counts (TSCs) above 25 million/ejaculate, while FSH levels were abnormally elevated in azoospermic subjects and some (not all) men with TSCs below 25 million/ ejaculate. The mean TSC of oligospermic men with elevated FSH levels was not statistically different from the mean TSC of men with normal FSH levels and sperm outputs below 25 million/ejaculate. Thus, the elevation of FSH levels observed in some oligospermic men was not related solely to decreased sperm counts. LH levels were higher in patients with TSCs below 25 million/ejaculate and high FSH levels than in men with TSCs below 25 million/ ejaculate and normal FSH levels. FSH levels were directly correlated with LH levels and negatively correlated with testosterone levels. These results suggest a relation between Leydig cell dysfunction and elevation of FSH levels in oligospermic men.
Estradiol‐induced Inhibition of Testosterone Production by Testicular Interstitial Cells Incubated In Vitro
Authors: GROTJAN H. E. , RODRIGUEZ‐RIGAU L. J. , STEINBERGER E.
Published: December 2015

Testosterone production by testicular interstitial cells incubated in vitro In the presence of 10−8 to 10−6 N 17β‐estradiol (E2), 17β‐estradiol‐3‐benzoate (E2B), or benzoic acid (B) was exmined. High concentrations of E2 (10−6 M), but not E2B or B, inhibited hCG‐induced testosterone production (∼20%), but only if E2 and hCG were added at the beginning of the incubation. Preincubation (2–6 hours) of interstitial cells with 10−6 to 10−8 M E2 did not alter hCG‐Induced steroidogenesis. The inhibitory action of E2 was characterized as a decrease in the testosterone production rate and a decrease in the response to a maximal dose of hCG but did not involve a shift in the hCG dose response curve. Under the conditions employed, interstitial cells did not metabolize E2. These results are consistent with the view that estrogens do not have a direct inhibitory effect on interstitial cell steroidogenesis during the first few hours after systemic injection.
Nuclear Uptake and Retention of Androgen by the Accessory Organs in the Male Golden Hamster
Authors: WEAKER F. J. , SHERIDAN P. J.
Published: December 2015

The nuclear uptake and retention of 3H‐dihydrotestosterone (3H‐DHT) were studied in the reproductive organs of the male hamster by autoradiography. Castrated adult male hamsters were infected with 0.2/μg of 3H‐DHT (107 Cl/mmole/100 g body weight) and sacrificed 1 1/2 hours later. The epididymides, prostate glands, and seminal vesicles were removed and processed for autoradiography. Localization of the androgen was observed in the nuclei of the secretory cells of all three organs. The nuclei of the smooth muscle cells of the muscularis and the connective tissue cells of these organs also demonstrated varying degrees of nuclear labeling. In addition, nuclear uptake was observed in the smooth muscle of the tunica media of the blood vessels of all three organs. In comparison to other studies, the results demonstrate species variation in the uptake of androgens in the accessory reproductive organs and support recent data that suggest that the cardiovascular system is a target organ for androgens.
Effects of Dibromochioropropane Upon Diurnal Variations of Gonadotropins and Androgens
Authors: CORTÉS‐GALLEGOS VICENTE , CASTAÑEDA GRACIELA , ALONSO ROCÍO , ARELLANO HORTENSIA , CERVANTES CARLOS , PARRA ADALBERTO
Published: December 2015

The effects of exposure to dibromochloropropane (DBCP) for one to seven years on testicular physiology were evaluated in five men by measuring the circulating levels of FSH, LH, androstenedione, testosterone, and dihydrotestosterone (DHT) every 4 hours throughout a 24‐hour period, and correlating this data with semen analysis and testicular biopsy. The study showed above‐normal concentrations of plasma FSH in 29 of 30 samples and plasma LH in 25 of 30 samples. With one exception, androstenedione levels were lower than normal in all subjects. Plasma testosterone and DHT concentrations were generally within the normal range (24 of 30 and 29 of 30, respectively). The anatomic damage to the testes varied from no perceptible lesions to complete absence of germinal epithelium, with the corresponding range of results of semen analysis from normal spermatogenesis to azoospermia. The results suggest that DBCP causes profound damage of the germinal epithelium and that damage may be present before a histologic abnormality can be clearly demonstrated. The observed elevated levels of LH in the face of normal testosterone concentrations would suggest damage to the Leydig cells, with the chronic overstimulation of these cells by LH being necessary to maintain essentially normal testosterone concentration. Histologic evidence of Leydig cell hyperplasia supports this interpretation of hormonal findings.
Interactive Effects of Ethanol and Δ9‐Tetrahydrocannabinol on Endocrine Functions in Male Mice
Authors: DALTERIO S. , BARTKE A. , SWEENEY C.
Published: December 2015

Exposure during sexual maturation to alcohol (ETOH) plus Δ9‐tetrahydrocannabinol (THC) significantly decreased the weights of adrenals, kidneys, testes, and emptied seminal vesicles ten days after cessation of treatment. Administration of ETOH alone reduced kidney weights, and that of THC alone decreased emptied seminal vesicle weights. The effects of THC treatment may be reversible, since mice killed 24 hours after the last exposure also had signifIcant reductions in kidney and testes weights. In contrast, perinatal exposure to ETOH or THC, alone or in combination, decreased testes weights in adulthood; THC alone reduced seminal weights, and ETOH or THC alone decreased kidney weights. Testosterone production in vitro was lower in testes obtained from mice perinatally exposed to ETOH, and plasma testosterone levels were reduced in all drug‐exposed animals. Plasma LH levels were lower and FSH levels higher in mice perinatally treated with the combination of ETOH plus THC. Postcastration LH and FSH levels were elevated in THC‐exposed mice. Exposure to ETOH or THC, alone or in combination, influences the development of male reproductive function in mice.
Early Ultra structural Findings in Experimentally Produced Varicocele in the Monkey Testis
Authors: FUSSELL E. N. , LEWIS RONALD W. , ROBERTS JAMES A. , HARRISON RICHARD M.
Published: December 2015

Varicocele was produced in adult male macaque monkeys (Macaca fascicularls) by partial occlusion of the left renal vein. Left varicoceie was verified by palpation. An increase In temperature of the left testicle was noted. Bilateral testicular biopsies were obtained at six, nine, and 18‐month intervals for morphologic studies. Early morphologic damage was not appreciated with the light microscope, but was found using transmission electron microscopy. The early ultrastructural damage consisted of loss in thickness and lamination of the basal lamina, cellular organelie degeneration, and enlargement of the intercellular spaces between basal cells of the seminiferous tubules. Later, ultrastructural damage was seen in the adluminal areas. At 18 months, ultrastructural damage had progressed to the right testis. Reflux of adrenal metabolites had no effect on the early ultrastructural damage.
Effects of Gossypol on the Reproductive System of Male Rats
Authors: HADLEY MARK A. , LIN YOUNG C. , DYM MARTIN
Published: December 2015

Gossypol acetic acid administered orally at 30 mg/kg body weight/day for five weeks inhibited the fertility of male rats without an apparent loss of libido. Sperm in the ejaculate were rendered immotile and were reduced in number. Serum testosterone and LH were reduced significantly from pretreatment values, whereas FSH values were not altered. Leydig cells from treated animals produced less testosterone than did control Leydig cells when incubated with LH. Furthermore, testosterone production by normal Leydig cells that were incubated with LH and gossypol was inversely related to gossypol concentration. Ultrastructural examination of epididymal spermatozoa revealed degeneration in the tail region, particularly in the mitochondrial sheath of the middle piece. Within the seminiferous epithelium, late spermatids displayed a similar degeneration, although not as severe. After a six‐week recovery period, normal fertility was re‐established and normal litters were produced. Sperm motility and number, serum testosterone and LH levels, and sperm structure all returned to normal.
Effect of Estradiol on the Rat Prostate in the Presence and Absence of Testosterone and Pituitary
Authors: LEE C. , PRINS G. S. , HENNEBERRY M. O. , GRAYHACK J. T.
Published: December 2015

In an attempt to elucidate the effect of estradiol on the rat prostate, four experiments were conducted. In experiment 1, rats were orchiectomized and were given subcutaneous implants of silastic capsules containing steroid hormones in the following five treatment regimens: empty capsule (C); capsule filled with 2 cm of testosterone (T‐2); T‐2 plus 0.5 cm of e‐tradiol (T‐2 + E‐0.5); T‐2 plus 2 cm of estradiol (T‐2 + E‐2); and T‐2 plus 5 cm of estradiol (T‐2 + E‐5). Three weeks later, no difference was noted in the ventral or the dorsal lobe of the prostate, but the lateral lobe was significantly heavier in animals treated with T‐2 plus various levels of estradiol than in those treated with T‐2 alone. Furthermore, serum levels of both estradiol and prolactin were significantly elevated in the groups treated with estrogen. Rats in experiment 2 were orchiectomized and hypophysectomized and were divided into two groups. One group was treated with T‐2 and another with T‐2 + E‐2. Three weeks later, weights of the three lobes of the prostate were not significantly different between the two groups. Although serum levels of estradiol were significantly higher in the T‐2 + E‐2 group than in the From the Department of Urology, Northwestern University Medical School, Chicago, Illinois T‐2 group, serum levels of prolactin were not significantly different. In experiment 3, rats were orchiectomized and hypophysectomized and were divided into two groups; one received E‐2, while the other received empty capsules. One week later, all three lobes of the prostate in E‐2‐treated animals were significantly heavier than the respective lobes in those receiving empty capsules. However, by three weeks weights of respective lobes were not significantly different between the two groups. To further investigate whether estradiol in the absence of testosterone and the pituitary has any stimulatory effect on the rat prostate, experiment 4 was carried out. Rats were orchiectomized and hypophysectomized; after three weeks, E‐2 or empty capsules were implanted. After one week of treatment with E‐2 or empty capsules, prostatic weights were not significantly different between the two groups. Results indicate that estradiol in the presence of testosterone and the functional pituitary has a stimulatory effect on the growth of the lateral lobe of the rat prostate. This stimulatory effect of estrogen was mediated through the pituitary. In the absence of testosterone and the functional pituitary, estradiol is unable to stimulate prostatic growth; rather, it delays the rate of castration‐induced regression in all three lobes of the rat prostate.
Abnormalities of the Hypothalamic—Pituitary—Leydig Cell Axis in Young Adult Rats with Vitamin A Deficiency
Authors: MENENDEZ CARLOS E. , DUCKETT GREGORY , ROOT ALLEN W.
Published: December 2015

The hypothalamic concentration of gonadotrophin releasing hormone (GnRH), the in vivo pituitary responses to GnRH, and the in vivo Leydig cell responses to bovine luteinizing hormone (LH) and to endogenous LH were determined in young adult male rats who had been on a vitamin‐A‐deficient (VAD) diet for 64 days and in age‐matched controls. Hypothalamic GnRH content was 3.06 ± 0.25 ng/hypothalamus in VAD (mean ± SEM) and 3.26 ± 0.25 ng/hypothalamus in controls. Baseline serum LH concentrations were 24.6 ± 4.7 ng/ml in VAD and 11.3 ± 2.3 ng/ml in controls (P < 0.02). Baseline serum follicle stimulating hormone (FSH) levels were 373 ± 61 ng/ml in VAD and 329 ± 16 ng/ml in controls. Fifteen minutes after administration of GnRH serum LH was 215 ± 16.3 ng/ml in VAD vs. 148 ± 18.3 ng/ml in controls (P <0.02). Serum FSH levels 15 minutes after administration of GnRH were 866 ± 67 ng/ml in VAD vs. 566 ± 58 ng/ml in controls (P < 0.01). Baseline serum testosterone (T) concentratio̊nswere 1.0 ± 0.2 ng/ml vs. 1.7 ± 0.3 ng/ml in controls (n.s.). Sixty minutes after exogenous LH administration, serum T concentrations were 21.7 ± 1.0 ng/ml in VAD vs. 17.8 ± 1.0 ng/ml in controls (P <0.05). Sixty minutes after administration of GnRH, which elevated endogenous LH serum concentrations, serum T concentrations were similar in both groups (7.8 ± 0.9 ng/ml for VAD vs. 9.7 ± 0.5 ng/ml for controls). The elevated serum LH concentrations, together with the increased pituitary responses to GnRH, are compatible with an appropriate hypothalamic‐pituitary response to a direct impairment in testicular function secondary to the VAD. However, the increased in vivo Leydig cell responses to exogenous LH stimulation in these young adult males with VAD remains unexplained.
Testis Vein Testosterone Falls in the Aging Rat: Refutation of “Dilution” Hypothesis
Authors: FRANKEL ARTHUR I. , MOCK EDWARD J.
Published: December 2015

A proposal that serum testosterone concentration declines during aging In the male laboratory rat because it is diluted in a larger body mass (and larger blood plasma volume) was reexamined. Five age groups were studied: 4, 7, 13, 19, and 24 months of age. Testosterone was measured in both testicular vein and peripheral serum collected from ether‐anesthetized rats within 2.5 minutes of removal from the cage. Both testosterone concentrations fell significantly (P < 0.001) at 7 months of age and did not change further in older rats, although body weight continued to increase until 19 months of age. The ratio of testicular vein to peripheral serum testosterone did not change significantly within the age span, although both concentrations (and their ratio) were at their lowest values at 24 months of age. Serum LH did not change significantly at any age. It was concluded that the decline in peripheral serum testosterone in the aging male rat reflects a significant change in testicular function, which first can be observed by 7 months of age. The eflect of dilution on testosterone and possibly on LH is a minor factor during aging.
Elevated Seminal pH and Ureaplasma Urealyticum
Authors: VALVO JOHN R. , CALDAMONE ANTHONY A. , HIPP SALLY , DUNCAN DAVID , COCKETT ABRAHAM T. K.
Published: December 2015

Normal semen has up to three polymorphonuclear leukocytes per high power field (HPF). Reduced zinc concentrations (<15 mg/dl), elevated pH (> 7.7), and neutrophi!s (5–10 leukocytes/HPF) in semen can suggest the presence of an asymptomatic infection. Reduced zinc levels, pyosemia and elevated pH suggest prostatic secretory dysfunction. Fifty‐seven patients with at least two of the above alterations underwent special urine and semen cultures in an attempt to isolate Ureaplasma (U.) urealyticum. Twenty‐seven of the 57 semen cultures were positive for U. urealyticum. Patients with pyosemia, reduced seminal zinc, and elevated pH should be treated with antibiotics (usually minocycline) for a minimum of four weeks. Subsequent semen analysis should be monitored to gauge efficacy of treatment. We emphasize a clinical therapeutic approach based on the above parameters, in the absence of other demonstrab!e causes of infertility.
A Comparison of Subjective and Objective Sperm Motility Evaluation
Authors: WALKER JON S. , WINET HOWARD , FREUND MATTHEW
Published: December 2015

A series of semen samples that had been recorded on motion picture film, then evaluated via standard visual techniques by a number of well established fertility clinics (Van Duijn et al (1971)), was analyzed frame‐by‐frame for sperm motility ratings with the aid of a movie reader‐computer image analysis system. Results of the latter analysis were considered an objective norm. Statistical comparison of the subjective and objective sets of data revealed that sperm % motility could be subjectively rated with reasonable accuracy when the percentage of sperm moving progressively at least 30 μm/second−2 was outside the range of 34–57. Within this range, however, there is a better than 93% chance for an erroneous subjective assessment. When the results of the computer method were compared with those of the spectrophotometric method of Atherton (1975), a poor correlation was obtained, indicating that if the latter method is an accurate measure of motility, it does not discriminate progressive motility.
Absence of a Sperm Coating Protein after Epididymovasostomy Report of One Case
Authors: WONG PATRICK Y. D. , TSANG ANGUS Y. F. , WANG CHRISTINA
Published: December 2015

Studies in animals indicate that epididymal sperm maturation requires the secretion of an epididymal protein that binds to the sperm surface. The possibility that this also occurs in man has been explored in the present study of one patient who was treated for bilateral obstruction of the cauda epididymis by epididymovasostomy. The patient's ejaculates obtained up to 18 months after surgery contained immotile sperm. Analysis of proteins in the seminal plasma revealed that the semen was deficient in a 38, 000 dalton protein found in seminal plasma of normal fertile men and in epididymal cytosol of patients with carcinoma of the prostate. This 38, 000 dalton protein also was found in sperm of normal men, but was absent in sperm of the patient. This observation supports the possibility that an epididymal protein coats the sperm surface during epididymal transit in man as well as in numerous other species.
Impact of Pulsatile Administration of Gonadotropin‐Releasing Hormone on the Pituitary‐Testicular Axis of the Immature Rat
Authors: MOGER WILLIAM H.
Published: December 2015

Effects of administering low doses of GnRH (30 ng/100 g body weight) at various frequencies on the pituitary‐testicular axis were investigated. During a 6‐hour treatment period, GnRH was administered to immature male rats at frequencies varying from once per 6 h to twice per hour. The frequency of GnRH administration was inversely related to increased serum LH and androgen concentrations, as well as to testicular testosterone and estradiol concentrations in response to the last GnRH injection. The capacity of the testes from GnRH‐treated animals to respond to LH in vitro was not impaired, suggesting that the reduced increase in serum androgen concentrations reflected reduced serum LH increase. Reduced serum LH increase in animals treated with GnRH twice per hour appears to be the result of a rapidly acting negative feedback effect of increased testicular androgen secretion early in the treatment period, since there was no decline in the serum LH response to GnRH in castrate, testosterone‐implanted animals treated with GnRH at this rate.
Human and Ram Seminal Plasma Both Contain a Calcium‐Dependent Regulator Protein
Authors: BRADLEY MARK P. , FORRESTER IAN T.
Published: December 2015

Biochemical aspects of post‐testicular sperm maturation have been studied. Partial purification of either human or ram seminal plasma yields a heat‐stable, acidic protein which is a Ca2+‐dependent regulator of 3′:5′‐cyclic nucleotide phosphodiesterase. This protein fraction has been provisionally named calsemin. Human calsemin activates the flagellar plasma membrane Ca2+‐ATPase of ram epididymal and ejaculated spermatozoa by 290% and 20%, respectively. Activation is abolished by trifluoperazine. The addition of calsemin plus Ca2+ to isolated ram caudal spermatozoa results in a three‐fold stimulation of flagellar beat activity. These results lead us to propose that only after interaction between calsemin and the sperm flagellar plasma membrane can the Ca2+‐ATPase obtain full expression to maximise Ca2+ efflux from the flagellum and thereby cause a stimulation and coordination of sperm flagellar beat activity. This finding may provide a partial biochemical explanation for the development of mammalian sperm motility.
Temporal Dissociation of Feedback and Direct Testicular Effects of Estradiol Benzoate in Male Rats
Authors: GROTJAN H. EDWARD , STEINBERGER EMIL
Published: December 2015

Studies were conducted to characterize the responses of the hypothalamic‐pituitary‐testicular axis to systemic injection of estradiol benzoate (EB) in the rat. Feedback effects of estrogens on the hypothalamic‐pituitary axis were assessed by changes in serum concentrations of LH whereas testicular androgen production was examined by in vitro testicular incubations in the presence and absence of 160 mIU hCG/2.2 ml. Injection of 50 μg EB reduced serum LH and serum testosterone to low levels by 2 hours and they remained low for up to 24 hours. One to 12 hours after EB treatment, testes were as responsive to hCG in vitro as were testes from rats receiving the vehicle. However, by 16 hours after EB injection, testicular responsiveness to hCG in vitro was reduced approximately 50%. Responses to chronic EB‐treatment (50 μg EB/d for 1 to 7 days) were characterized in mature hypophysectomized males. Testicular incubates from hypophysectomized EB‐treated males contained less testosterone than those from corresponding oil‐treated control groups. In addition, testes of hypophysectomized EB‐treated males were less responsive (±50%) to hCG in vitro, suggesting a direct effect of estrogens mediated at the testicular level. Thus, injection of estrogens to intact males reduces serum LH which, in turn, rapidly reduces serum and testicular testosterone. By 16 hours after injection, estrogens may also exert a direct effect on the testis to decrease testicular responsiveness to hCG/LH. Thus, there is a temporal dissociation of feedback and possible direct testicular effects in EB‐treated males, both of which act to inhibit steroidogenesis. The reduction in LH occurs approximately 14 to 22 hours before the direct effect of estrogens on the testis is evident.
A Case of Bilateral Absence of the Vas Deferens and the Body and Tail of the Epididymis in Association with Multiple Congenital Anomalies
Authors: CHRISTENSON PAUL J. , FOURCROY JEAN L. , O'CONNELL KEVIN J.
Published: December 2015

A patient presenting with infertility was found to have bilateral agenesis of the vas deferens and body and tail of the epididymis in association with cleft mitral valve, epiphyseal dysplasia, polydactyly, high arched palate, and partial syndactyly of two toes. Two of the patient's siblings were also affected with similar abnormalities.
Relationship Between Fertilizing Ability and cAMP in Human Spermatozoa
Authors: PERREAULT SALLY D. , ROGERS B. JANE
Published: December 2015

The goal of this study was to investigate the relationship between cAMP and the fertilizing ability of human spermatozoa. Levels of cAMP were measured in human spermatozoa during 6‐hour in vitro incubation in capacitation medium, in both the presence and absence of phosphodiesterase (PDE) inhibitor. The fertilizing ability of the same samples was assayed with zona‐free hamster eggs. In the absence of PDE inhibitor, no relationship was apparent between mean cAMP levels, which remained at 3–4 pmol cAMP/107 spermatozoa, and mean fertilizing ability, which increased from 4% at the start of the incubation to 33% at 6 hours. In the presence of PDE inhibitor (7 mM caffeine or 10 mM theophylline), cAMP concentrations increased within minutes to 3–4 times control levels. Despite this increase in cAMP, there was no immediate change in fertilizing ability. This was true whether PDE inhibitor was present from the start or added to control sperm after 6 or 22 hours of incubation. However, once the sperm were exposed to PDE inhibitor for 4–6 hours, they fertilized a significantly greater proportion of eggs than did control samples. These results suggest that PDE inhibitors, or elevated cAMP levels, do not immediately induce the acrosome reaction, but rather appear to reduce the amount of time required for capacitation to occur in vitro.
Characterization of the Sperm Penetration Bioassay
Authors: WOLF DON P. , SOKOLOSKI JOSEPH E.
Published: December 2015

Parameters influencing the zona‐free hamster egg bioassay for human sperm fertility potential were evaluated. Egg recovery from hamsters superovulated at random with respect to their estrous cycle was enhanced when the PMS‐HCG time interval was lengthened. Prolonged egg exposure to trypsin during zona removal did not adversely affect egg viability. A swim‐up procedure for washing human sperm was superior to a centrifugation‐resuspension technique, although the yield of washed cells was low. The kinetics of sperm capacitation were examined for six different donors over a 22‐hour time period. Capacitation in 0.3% albumin was maximal after 6.5 hours, and penetration scores in five of the six donors declined thereafter. In 3.5% albumin, capacitation was slower with peak penetration levels observed at 13.5 hours. Much higher penetration was noted when sperm, capacitated in 3.5% albumin, were compared with those exposed to 0.3%. Specific recommendations for optimizing bioassay outcome are summarized.
Testosterone Metabolism by Testicular Tissue
Authors: AHMAD NAZIR , WARREN DWIGHT W.
Published: December 2015

Teased testicular tissue with defined cell populations from experimental rats, as well as testicular tissue from normal rats, was incubated in an environment that insured the morphologic integrity of the tissue at the conclusion of the experiment. In cryptorchid animals, conversion of available substrate to various metabolites by testicular tissue comprised of Leydig and Sertoli cells was comparable to that of intact controls. Using hypophysectomized and hypophysectomized‐cryptorchid rats, reliably measurable androgen metabolites were produced by testicular tissue that had specific populations of intact cell types. The reported methodology shows that defined cell populations, capable of testosterone metabolism, can be obtained in vivo by surgical procedures. Histologic monitoring of the tissue at the conclusion of the incubation has helped define the best environment for the maintenance of morphologic integrity throughout the incubation period. These techniques will allow future work on quantitative assessment of testosterone metabolism by defined cell populations of the testis.
Enhanced Daily Sperm Production in the Remaining Testis of Aged Rats Following Hemicastration
Authors: JOHNSON LARRY , NEAVES WILLIAM B.
Published: December 2015

To investigate the effects of age and hemicastration on daily sperm production (DSP), testes from adult (6 to 10 months) and aged (22 to 24 months) Sprague‐Dawley rats were evaluated before and four months after hemicastration. Testes were weighted, decapsulated, homogenized in a Waring Blender, and evaluated for the number of maturation‐phase spermatids in the homogenates. DSP per testis was calculated by dividing the number of spermatids in the homogenates by the estimated life span of the spermatids (6.3 days). The same testicular traits, along with plasma LH and FSH levels, were determined in a second group of aged rats. Considering both testes in the first experiment, neither DSP per testis nor DSP per g parenchyma were significantly affected by age. However, the age testis interaction was significant (P < 0.01) in both parameters. DSP per g of the testis removed at hemicastration was slightly lower (P < 0.05) in the aged group, and DSP per g in the aged rat was enhanced (P < 0.05) in the hemicastrates. Unlike the adults, aged rats had enhanced (P < 0.01) DSP per testis in the remaining testis posthemicastration. In the second experiment, testicular weight, DSP per g, and DSP per testis were enhanced (P < 0.01) after hemicastration. Plasma FSH levels were significantly (P < 0.01) elevated within one week after hemicastration and remained elevated four months later. Plasma LH levels were not elevated within one week after hemicastration but were significantly (P < 0.01) elevated four months following hemicastration.

We concluded that: 1. measured by DSP, no decline in spermatogenesis was found between 6 to 10 and 22 to 24 months of age; 2. aged rats were capable of hemicastration‐induced testicular enlargement and enhancement of DSP, 3. rats in the adult group were not capable of these hemicastration‐induced changes, 4. posthemicastration testicular enlargement was accompanied by an increased number of germ cells; 5. immediate and continued elevation of plasma FSH suggests its involvement in hemicastration‐induced testicular enlargement of aged rats.
Testicular Responsiveness to a Single Dose of hCG During Chronic Hyper‐ and Hypoprolactinemia in Aged Men
Authors: MARTIKAINEN HANNU , HUHTANIEMI ILPO , MYLLYLÄ VILHO , SOTANIEMI KYÖSTI , NUMMI KARI , VIHKO REIJO
Published: December 2015

In order to characterize the long‐term effects of elevated or lowered serum prolactin levels on testicular endocrine function, peripheral serum FSH, LH, prolactin, testosterone, 17‐hydroxyprogesterone, and estradiol concentrations were determined in hyper‐ and hypoprolactinemic men (treated with neuroleptics versus dopamine agonists), 50 to 80 years of age, in the basal state and after a single intramuscular injection of 5000 IU hCG. Prior to hCG injection, the concentrations of testosterone and 17‐hydroxyprogesterone were significantly lower in hyper‐ than in hypoprolactinemic men (P < 0.02); but estradiol, LH, and FSH levels were not significantly different between the two groups investigated. In hyperprolactinemic men, hCG induced a significant increase (196 ± 40%, SE,P < 0.05) in the mean maximum serum testosterone concentration at 2 to 4 days; whereas in the hypoprolactinemia group, the maximum androgen response was 162 ± 11%. The significant androgen response seen during chronic hyperprolactinemia was associated with a smaller increase in estradiol concentration (274 ± 44% versus 472 ± 78%, P0.05) at 1 to 2 days after hCG injection as compared with the hypoprolactinemia group. The behavior of 17‐hydroxyprogesterone was similar in both groups. Following hCG injection, serum FSH showed a tendency to decrease in both groups.

The present results suggst differences in testicular function during hyper‐ and hypoprolactinemia, and indicate that prolactin may regulate testicular androgen synthesis at several steps. In the basal state (before hCG administration), testosterone output of hyperprolactinemic men appears to be reduced by inhibition of one or more steps, as yet unidentified, in the biosynthetic pathway proximal to C21 steroid side‐chain cleavage. During hCG challenge, however, partial inhibition by hyperprolactinemia of testicular aromatization may offer an explanation for the major testicular androgen response to gonadotropin stimulation, when compared with the low pretreatment levels of testosterone.
Individual Differences in LH and FSH Responses to Orchidectomy and Testosterone Replacement Therapy in Rams
Authors: D'OCCHIO M. J. , SCHANBACHER B. D. , KINDER J. E.
Published: December 2015

Profiles of LH and FSH levels and pituitary LH responses to exogenous luteinizing hormone releasing hormone (LHRH) have been characterized in rams, castrated rams (wethers), and wethers implanted with testosterone. Rams were castrated when adult, and, at the time of castration, two groups of wethers were implanted with either four or eight testosterone capsules. Rams showed random pulses of LH and testosterone which were temporally related. The number of LH and testosterone pulses per 24 hours differed among rams, giving rise to large differences in the mean levels of these hormones. Mean FSH levels and pituitary LH responses to LHRH also differed among rams and were positively correlated to differences in LH levels. All three nonimplanted wethers showed a rhythmic pulsatile pattern of LH secretion and had elevated mean LH and FSH levels. There were, however, appreciable differences between wethers with regard to mean LH and FSH levels and pituitary LH responses to LHRH. Both four and eight testosterone capsules were effective in suppressing pulsatile LH secretion and mean LH and FSH levels in two out of three wethers. In a third animal within each of these groups, however, LH and FSH profiles and LH responses to LHRH were characteristic of nonimplanted wethers. These data suggest that individual rams have different inherent capacities to secrete gonadotropins which influence LH and FSH responses to castration and testosterone replacement therapy.
Immunocytochemical Localization of Acrosin on Both Acrosomal Membranes and in the Acrosomal Matrix of Porcine Spermatozoa
Authors: JOHNSON L. A. , GARNER D. L. , TRUITT‐GILBERT ANNE J. , LESSLEY B. A.
Published: December 2015

Immunocytochemical techniques were employed to determine, at the ultrastructural level, the location of acrosin in porcine spermatozoa. Antisera to highly purified porcine acrosin was produced in rabbits. The (Fab')2 fragments of the immunoglobulins were purified and conjugated with horseradish peroxidase (HRP). Washed, formaldehyde‐fixed spermatozoa were reacted with the labeled antiacrosin immunoglobulins, utilizing a direct staining technique. Electron microscopy revealed that the peroxidase reaction product of HRP‐antiporcine acrosin was distributed evenly over the outer acrosomal membrane of spermatozoa with intact acrosomes. The labeled antibody was also distributed evenly over the inner acrosomal membrane of cells when the overlying acrosomal structures were absent. In some spermatozoa, labeling was noted throughout the acrosomal matrix. No significant labeling was observed in control specimens when spermatozoa were exposed to HRP‐antiporcine acrosin immunoglobulins that had been adsorbed previously with excess purified acrosin or exposed to HRP‐conjugated rabbit antiporcine immunoglobulins. This pattern of labeling is consistent with die hypothesis that acrosin may function as a zona lysin. The observation that the outer acrosomal membrane and acrosomal matrix are labeled suggests that acrosin is not exclusively located on the inner acrosomal membrane and, thus, could participate in physiologic events other than zona penetration.
Ultrastructure and Intercellular Vacuolization of Isolated Perfused and Control Rat Testes
Authors: HOFFER ANITA P. , CARLTON BETSY D. , BRUNENGRABER HENRI
Published: December 2015

Isolated rat testes perfused in closed circuit with albuminated Krebs‐Ringer bicarbonate buffer were examined by light and electron microscopic techniques in order to assess the structural integrity of the model. The extent of intercellular vacuolization in perfused testes was similar to that of control testes that had been prepared for electron microscopy by routine methods of perfusion fixation. The isolated perfused testes exhibit excellent preservation at the light and electron microscope level. The results indicate that albuminated Krebs Ringer bicarbonate buffer is an excellent perfusate for in vitro studies of the isolated rat testis. This model of perfused testis can be used to study the early pathology of the effects of toxic compounds on the microscopic anatomy of the male gonad.
The Effect of Testicular X‐irradiation on Spermatogenesis in Man
Authors: CLIFTON DONALD K. , BREMNER WILLIAM J.
Published: December 2015

Existing data concerning the effects of x‐irradiation on spermatogenesis in man were analyzed and the results were compared to published data on the mouse. Testicular x‐irradiation produced a transient, but substantial, suppression of sperm counts in man, with an ED50 near 11 rad. The length of time to recovery was proportional to the irradiation dose. The ED50 for suppression of type A spermatogonia following radiation exposure in man was similar (9.7 rad), although the response curves for spermatogonia and sperm count were not parallel. The effect of irradiation on type A spermatogonia in the mouse was parallel to that found in man, but with an ED50 of 30.0 rad. These results suggest that, compared to the mouse, spermatogenesis in man is approximately 3.1 times more sensitive to ionizing irradiation.
Tubulovasostomy in the Rat A New Experimental Model
Authors: BELGRANO EMANUELE , CARMIGNANI GIORGIO , PUPPO PAOLO , GABOARDI FRANCO , TROMBETTA CARLO
Published: December 2015

Tubular patency is the primary concern in the evaluation of procedures for epididymovasostomy. The epididymal lumen easily becomes occluded or obstructed, with the resulting recurrence of azoospermia. Recently, twolayer direct anastomosis has been advocated. The aim of the present study was to present an experimental model of tubulovasostomy in the rat. Microsurgery was performed in 18 rats (16–40 × magnification). Suture material used was 11/0 Vycryl® or nylon for the internal layer of the anastomosis and 10/0 Ethilon® for the external layer. After 6 and 12 weeks, semen samples were obtained by electroejaculation and evaluated for sperm count and motility.