bluuebunny/crossref_metadata_2025 huggingface dataset:
How Much Does Social Status Matter to Longevity?—Evidence from China's Academician Election
Authors: Liu Gordon G. , Kwon Ohyun , Xue Xindong , Fleisher Belton M
Published: December 2015

We provide evidence for the causal impact of social status on longevity by exploiting a natural experiment in which subjects undergo a shift in their social status without considerable economic impact. We gather data on 4190 scientists who were either nominated for or successfully elected to the Chinese Academy of Science or of Engineering. Being elected as an academician in China is a boost in social status (vice‐ministerial level) with negligible direct economic impact (US$30 monthly before 2009). After correcting for two sources of bias, (1) some potential academicians decease too young to be elected, leading to selection bias in favor of academicians and (2) the endogenous relationship between health and social status, we find that the enhanced social status of becoming an academician leads to approximately 1.2 years longer life. Copyright © 2015 John Wiley & Sons, Ltd.
Use of propranolol for parotid hemangioma
Authors: Chang Lei , Jin Yunbo , Lv Dongze , Ying Hanru , Wang Tianyou , Qiu Yajing , Ma Gang , Chen Hui , Yu Wenxin , Yang Xi , Lin Xiaoxi
Published: December 2015

Background

Few specific reports have addressed propranolol as a treatment for parotid hemangioma, and its mechanism remains unclear.

Methods

Eighty‐seven patients were recruited in this prospective study. Ten patients underwent detailed color Doppler examination. The depths, vessel densities, and resistant indices of 10 lesions were recorded and analyzed before treatment and at 1 and 3 months after treatment.

Results

The overall responses were “bad” in 2 cases, “stable” in 4 cases, “good” in 53 cases, and “excellent” in 28 cases. Hemangioma regrowth was observed in 11 cases (12.6%). The parents of 18 patients (20.7%) complained that their children experienced minor discomfort during therapy. The lesion depths, vessel densities, and resistant indices were altered after propranolol treatment.

Conclusion

Propranolol can significantly reduce the sizes of parotid hemangiomas with minor side effects. Hemodynamic changes might play an important role in the course of propranolol treatment. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1730–E1736, 2016
PRISM: Phase 2 trial with panitumumab monotherapy as second‐line treatment in patients with recurrent or metastatic squamous cell carcinoma of the head and neck
Authors: Rischin Danny , Spigel David R. , Adkins Douglas , Wein Richard , Arnold Susanne , Singhal Nimit , Lee Oliver , Murugappan Swami
Published: December 2015

Background

Panitumumab Regimen In Second‐line Monotherapy of Head and Neck Cancer (PRISM) trial evaluated the safety and efficacy of panitumumab as second‐line monotherapy in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN).

Methods

This was an open‐label, single‐arm, multicenter trial that enrolled patients with progressive disease or intolerance to first‐line systemic chemotherapy for recurrent or metastatic SCCHN. Patients received panitumumab 9 mg/kg Q3W. The primary endpoint was overall response rate; secondary endpoints included disease control rate, overall survival (OS), progression‐free survival (PFS), and safety.

Results

The overall response rate was 4% (2 of 51 patients) and the disease control rate was 39% (20 of 51 patients). Median PFS was 1.4 months (95% confidence interval [CI] = 1.3–2.4 months). Median OS was 5.1 months (95% CI = 4.3–8.3 months). The most common adverse events were rash/dermatitis acneiform (69%), fatigue (33%), dry skin (21%), and hypomagnesemia (21%). There was one treatment‐related death (angioedema).

Conclusion

Panitumumab monotherapy had limited activity in previously treated patients with recurrent or metastatic SCCHN. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1756–E1761, 2016
IR's Role in Piloting an Assessment Model: Coordination, Consultation and Compromise
Authors: Sweatman Robert A.
Published: December 2015

This chapter focuses on IR's role in coordinating a pilot of the Degree Qualifications Profile (DQP) for assessment in a new master's degree program and provides guidance on frameworks that can be used, important technical considerations, and ways IR can be involved to advance the use of rubrics as a primary program assessment tool.
Research Competencies in Counseling: A Delphi Study
Authors: Wester Kelly L. , Borders L. DiAnne
Published: December 2015

Research quality has become the focus of a nationwide discussion, one from which the counseling field is not exempt. One hindrance to improving counseling research is the lack of guidelines for research competence. The purpose of this study was to develop an initial list of research competencies for the counseling field using the Delphi method. An expert panel of counseling researchers reached consensus on 159 research competencies. Suggestions for implementation and future research are discussed.
The Development and Experience of Combat‐Related PTSD: A Demand for Neurofeedback as an Effective Form of Treatment
Authors: Fragedakis Tami Maes , Toriello Paul
Published: December 2015

Veterans experience a considerable course of posttraumatic stress disorder (PTSD), and because of several psychosocial issues, traditional interventions and traditional intervention settings are ineffective for this population. A new cutting‐edge approach, known as neurofeedback, trains clients to control and manipulate their central nervous system and ameliorate physiological symptoms of stress disorders. The authors delineate how neurofeedback can be an effective and innovative intervention for PTSD experienced by the military population.
Metronidazole: In Vitro Activity, Pharmacology and Efficacy in Anaerobic Bacterial Infections
Authors: Tally Francis P. , Sullivan C. Edmond
Published: December 2015

Metronidazole is a 5‐nitroimidazole that has selective activity against anaerobic microorganisms, including bacteria and protozoa. Intravenous metronidazole has recently been approved by the U.S. Food and Drug Administration for the treatment of serious anaerobic bacterial infections. It is usually bactericidal at low concentrations, and its spectrum of activity encompasses almost all anaerobic bacteria and some capnophilic organisms. Anaerobic bacteria known to be resistant to metronidazole include occasional anaerobic cocci, some nonsporulating gram‐positive bacilli and propionibacterium. Metronidazole is the most active antimicrobial agent against Bacteroides fragilis, the most resistant of anaerobic bacteria. Kill‐curve studies demonstrate that there is a 2 to 5 log decrease in the number of colony forming units of S. fragilis and Clostridium perfringens within one hour. The only well documented metronidazole‐resistant strain is a B. fragilis isolated from the normal flora of a patient on long‐term metronidazole therapy for Crohn's Disease. Metronidazole resistance in Trichomonas vaginalis has recently been described in a few strains that are able to survive at increased oxygen tensions. Metronidazole has been shown to be efficacious in certain protozoal infections including trichomonal vaginitis, extraintestinal amebiasis, and giardiasis. Clinical studies have shown metronidazole to be efficacious in the therapy of a variety of anaerobic infections, including non‐traumatic brain abscesses, intraabdominal sepsis, pelvic suppuration and necrotizing soft tissue infections. There have been disappointing results in the therapy of anaerobic pleuropulmonary infections with a number of superinfections caused by aerobic bacteria. Since metronidazole lacks any activity against aerobic bacteria, it must be combined with other agents, usually aminoglycosides, in the treatment of mixed infections involving anaerobic and aerobic bacteria.
Clonidine in Opiate Withdrawal: Review and Appraisal of Clinical Findings
Authors: Washton Arnold M. , Resnick Richard B.
Published: December 2015

Studies in animals and humans have demonstrated that clonidine hydrochloride, an alpha‐2‐nor‐adrenergic agonist, significantly attenuates the opiate withdrawal syndrome. Inpatient and outpatient clinical studies have shown that clonidine is a reasonably safe, specific, and effective agent for detoxifying opiate addicts. Clonidine seems best suited for use as a transitional treatment between opiate dependence and induction onto the opiate antagonist naltrexone. Dosage regimens of clonidine must be individualized according to symptoms and side effects and closely supervised because of varying sensitivity to clonidine's sedative, hypotensive, and withdrawal‐suppressing effects. Clonidine is an important new treatment option for selected opiate addicts and may be the treatment of choice when detoxification using methadone is inappropriate, unsuccessful, or unavailable. Lofexidine, a structural analogue of clonidine, may be safer and more effective as an opiate detoxification treatment. It has similar withdrawal‐suppressing actions but causes little hypotension and sedation. Although clonidine and lofexidine may be highly effective in helping opiate addicts achieve initial abstinence, a multi‐modality aftercare treatment approach including naltrexone and psychotherapy may be necessary to maintain an abstinent state.
Antimicrobial Activity, Pharmacokinetics, Adverse Reactions, and Therapeutic Indications of Cefoperazone
Authors: Funk Elizabeth A. , Strausbaugh Larry J.
Published: December 2015

Cefoperazone is a parenteral cephalosporin antibiotic that is pending approval by the U. S. Food and Drug Administration. Compared to most other cephalosporins cefoperazone has a greatly expanded spectrum of bactericidal activity that encompasses most aerobic gram‐positive bacteria except entero‐cocci, most aerobic gram‐negative bacteria, including a majority of Pseudomonas aeruginosa strains, and a number of pathogenic anaerobic bacteria. Its long serum half‐life, approximately two hours, permits a twelve hourly dosing schedule. No dosage modification is required in patients with renal insufficiency, and only minor modification is needed in patients with hepatic insufficiency or biliary obstruction. Clinical trials have established cefoperazone's efficacy in lower respiratory tract infections, urinary tract infections, and a variety of other bacterial infections. Adverse reactions have been infrequent, and few serious reactions have been identified. Cefoperazone is a promising new agent for the treatment of gram‐negative bacillary and polymicrobial infections, especially in settings that require empiric therapy.
Pharmacology, Clinical Efficacy, and Adverse Effects of the Nonsteroidal Anti‐Inflammatory Agent Benoxaprofen
Authors: Dahl Stephen L. , Ward John R.
Published: December 2015

Benoxaprofen is a nonsteroidal anti‐inflammatory agent that belongs to the arylalkanoic acid class of antirheumatic drugs. Animal studies have demonstrated that it has analgesic, antipyretic, and antiinflammatory properties. Although benoxaprofen is a relatively weak inhibitor of cyclo‐oxygenase in in vitro systems, inhibits lipoxygenase in other systems, and inhibits monocyte migration in some animal models of inflammation, it has not been established that it is unique with regard to these actions. Benoxaprofen undergoes hepatic metabolism via glucuronidation as the primary route of elimination and has a half‐life of 28–35 hr. Clinical trials have demonstrated that its analgesic and anti‐inflammatory properties are useful in the management of the signs and symptoms of rheumatoid arthritis and osteoarthritis. Once daily dosing of 300–600 mg is effective for many patients. In addition to gastrointestinal intolerance, photosensitivity and onycholysis are the most frequent adverse effects encountered. Recent reports of fatal cholestatic jaundice often associated with nephrotoxicity led to the withdrawal of benoxaprofen from world markets. It is uncertain whether it will once again be available for clinical use.
Pirbuterol Hydrochloride: Evaluation of Beta Adrenergic Agonist Activity in Reversible Obstructive Pulmonary Disease and Congestive Heart Failure
Authors: Weber Richard W. , Nelson Harold S.
Published: December 2015

Pirbuterol hydrochloride is a beta2 adrenergic agonist with a structure similar to that of albuterol, except for the substitution of a pyridine ring for the benzene ring. It is comparable in duration of action to albuterol when given by inhalation, but it is threefold less potent by weight. In man, pirbuterol and albuterol have similar beta2 selectivity. In the acute therapy of chronic obstructive pulmonary disease, pirbuterol is most effective in oral doses of 15–20 mg, and by aerosol in doses of 400 μg or greater. Long‐term studies of oral pirbuterol in doses between 30–60 mg/day are promising, but further research is warranted. The combination of pirbuterol's beta2 and lesser beta1 activity has proven helpful in the therapy of refractory congestive heart failure. Improvement of function of both right and left ventricles and systemic and pulmonic circulations has been demonstrated acutely. Drug effect wanes, as with other beta adrenergic agonists, due to the development of tolerance; however, long‐term benefit appears to persist in both pulmonary and cardiac patients. Pirbuterol will be marketed in the United States as 10 and 15 mg tablets and as a 200 μg per actuation metered dose aerosol for use in pulmonary patients only; it will not be approved for use in congestive heart failure. In terms of beta2 selectivity, duration of action, potency and frequency of side effects, pirbuterol is comparable to the two beta2 agonists already available in the United States, albuterol and terbutaline.
Amsacrine (m‐AMSA): A New Antineoplastic Agent Pharmacology, Clinical Activity and Toxicity
Authors: Hornedo Javier , Van Echo David A.
Published: December 2015

The synthetic aminoacridine derivative amsacrine (m‐AMSA) is capable of preventing DNA from serving as a template in replication and DNA synthesis. This mechanism of action is similar to that of anthracyclines, but clinical evidence suggests the lack of cross‐resistance. The recommended dosage in patients with solid tumors is 90–120 mg/m2 intravenously every 3–4 weeks. Despite the initial encouraging reports from experimental models, m‐AMSA has shown no real impact in the treatment of patients with a wide variety of solid tumors. In relapsed acute nonlymphocytic leukemia, 20–30% of patients will achieve complete remission. An increased remission rate is obtained when m‐AMSA is combined with other agents, especially with high‐dose cytosine arabinoside, with a complete remission rate of 50–60% in relapsed patients. Currently, several phase III trials are evaluating m‐AMSA combinations against daunorubicin‐containing regimens in patients with previously untreated acute leukemia. The potential role of these regimens in this disease remains to be defined.
Acute Hepatotoxicity After Excessively High Doses of Carbamazepine on Two Occasions
Authors: Luke David R. , Rocci Mario L. , Schaible Deborah H. , Ferguson Roger K.
Published: December 2015

A 2½‐year‐old child being treated with carbamazepine (CBZ) for a seizure disorder on two separate occasions experienced elevated CBZ serum concentrations (28 and 23.2 mg/L), severe liver damage (SGOT > 6000 IU, SGPT > 5000 IU), and central nervous system manifestations (coma, lethargy, seizures). During the first episode, the time course of CBZ concentrations exhibited a nonlinear decline and was accompanied by CBZ‐10,11‐epoxide concentrations that were elvated 4‐fold compared to normal values. Cerebrospinal fluid concentrations of CBZ and CBZ‐10,11‐epoxide were also elevated, although their ratios to serum concentrations did not suggest enhanced permeability of the central nervous system to these substances. The concentrations of CBZ‐10,11‐epoxide but not CBZ were elevated for the duration of time that the patient was comatose, suggesting that this metabolite may contribute to the neurotoxic side effects observed with CBZ therapy.
Analgesic Effect of an Aspirin‐codeine‐butalbital‐caffeine Combination and an Acetaminophen‐codeine Combination in Postoperative Oral Surgery Pain
Authors: Forbes James A. , Jones Katherine F. , Smith W. King , Gongloff Charles M.
Published: December 2015

The efficacy of an aspirin‐caffeine‐codeine‐butalbital combination was compared to an acetaminophen‐codeine combination and placebo in outpatients who had moderate or severe pain after the surgical removal of impacted third molars. Using a self‐rating record, patients rated their pain, relief, anxiety and relaxation hourly for up to 6 hours after medicating. Each active medication was significantly superior to placebo for measures of analgesia and relaxation. Although the butalbital‐containing combination provided consistently greater analgesia, the differences between active medications were not statistically significant. The acetaminophen‐codeine combination significantly reduced anxiety; however, the butalbital containing combination did not. The results of this study suggest that female patients may have greater efficacy than male patients. All adverse effects were transitory and consistent with the known pharmacologic profiles of the study medications or the backup analgesic.
Analgesic Efficacy of Low‐dose Ibuprofen in Dental Extraction Pain
Authors: Jain Adesh K. , Ryan Jerome R. , McMahon F. Gilbert , Kuebel J. O. , Walters P. J. , Noveck Cynthia
Published: December 2015

A single‐dose, double‐blind, randomized, parallel trial was conducted to compare the analgesic efficacy of oral ibuprofen (I) 100, 200, or 400 mg, aspirin (ASA) 650 mg, and placebo in moderate to severe pain after extraction of impacted teeth. Subjective, self‐evaluated pain intensity and pain relief reports, hourly for 6 hours, were used as indexes of analgesic response. Data on 227 evaluable patients showed significant differences among the 4 active treatments and placebo (p < 0.001) by most measurements of analgesia. Although no consistent, significant differences were observed among the active drugs, I 400 mg performed the best, followed by I 200 mg, ASA 650 mg, and I 100 mg. Remedication was required by 59% patients receiving I 400 mg, 67% taking I 200 mg, 73% taking ASA 650 mg, 74% taking I 100 mg, and 96% receiving placebo. Differences between I 400 mg and I 100 mg were significant for remedication data (p < 0.05). Side effects were minor, infrequent, and not dose related. In this study, I 100 mg was distinctly superior to placebo and probably as effective as ASA 650 mg in relieving pain. Only a shallow dose response of ibuprofen was observed.
Monoclonal Antilymphocyte Antibody (OKT3) Treatment of Acute Renal Allograft Rejection
Authors: Canafax Daniel M. , Draxler Cheryl A.
Published: December 2015

Recent advances in immunosuppressive therapy have dramatically improved the survival rates for recipients of organ allografts by reducing the frequency of rejection. Cyclosporine, azathioprine, and prednisone for immunoprophylaxis are especially effective. When rejection occurs, the treatment usually includes high doses of oral or intravenous corticosteroids, antilymphocyte globulin, or antithymocyte globulin. A new monoclonal antilymphocyte antibody, OKT3, promises to improve allograft survival rates further.
Acute Bacterial Endocarditis Due to Hemophilus parainfluenzae Response to Ceftizoxime in an Ampicillin‐allergic Patient
Authors: da Camara Carlos C. , Weiner Bruce , Stetz Joseph J.
Published: December 2015

Endocarditis secondary to Hemophilus parainfluenzae is an uncommon entity that appears to be increasing in frequency, perhaps due to improved laboratory isolation techniques. Although controversial, most of the published literature recommends a penicillin, with or without concomitant gentamicin, as definitive therapy. We report the first successful use of the third‐generation cephalosporin ceftizoxime in an ampicillin‐allergic patient. A 55‐year‐old white female was hospitalized after 5 days of experiencing fever, chills, nausea, and vomiting. A cardiac echocardiogram revealed a large mitral valve vegetation, and the patient was treated with intravenous ampicillin, gentamicin, and clindamycin. Two weeks after emergency mitral valve replacement the patient developed spiking fevers and a macular, erythematous rash while receiving ampicillin. Ceftizoxime was initiated and continued to complete a 4‐week period of intravenous antibiotics. Follow‐up at 14 months showed no further evidence of infection. Ceftizoxime appears efficacious in eradicating H. parainfluenzae in patients allergic to penicillin.
A Review of Lithium Dosing Methods
Authors: Lobeck Frank
Published: December 2015

Lithium's narrow therapeutic range, concentration‐effect relationship, and large differences in interindividual disposition make it an attractive candidate for predictive dosing methods. Lithium disposition is influenced by a number of factors, including patient characteristics, renal function, and concomitant drug therapies. These factors are accounted for, in varied degrees, in the different dosing methods available. One a priori method takes many of these factors into account and appears to have better reliability than others that ignore nonrenal influences on lithium disposition. The lack of data on pharmacokinetic values in different populations limits the usefulness of many of the single‐point methods. Better data on the disposition of lithium in differing populations would greatly enhance the utility of both the a priori and single‐point methods. Several multipoint methods, which estimate an individual's pharmacokinetic values, have also been described. These appear to be the most reliable, although they are time consuming and may delay the initiation of therapy. A well‐designed Bayesian approach to the dosing of lithium, although not currently available, would be the most useful.
Hepatotoxicity Associated with Amiodarone Therapy
Authors: Flaharty Kristen K. , Chase Sandra L. , Yaghsezian Harout M. , Rubin Raphael
Published: December 2015

Amiodarone has been reported to cause asymptomatic increases in liver function tests in 15 — 55% of patients. Clinically apparent, symptomatic hepatic disease occurs less frequently, but patients have been reported to have hepatomegaly, jaundice, cirrhosis, or chronic active hepatitis. Less well recognized is the fact that amiodarone has been attributed to six deaths. We cared for a patient with amiodarone hepatotoxicity, which led us to review the literature associated with this serious condition.
Clinical Studies in an Adult Male Patient with “Isolated Follicle Stimulating Hormone (FSH) Deficiency”
Authors: MOZAFFARIAN G. A. , HIGLEY M. , PAULSEN C. A.
Published: December 2015

Previous reports concerning isolated follicle stimulating hormone (FSH) deficiency and its possible pathogenesis have been conflicting. Both “normal” and “abnormal” FSH response to luteinizing hormone releasing hormone (LHRH) infusion have been described. We studied a 22‐year‐old man with normal basal serum testosterone and luteinizing hormone (LH) levels but undetectable levels of serum FSH. His serum LH titers showed one secretory spike during a 4‐hour sampling at 20‐minute intervals, whereas his serum FSH titers remained undetectable (<0.4 IU/1). Infusion of LHRH, 0.2 μg/minute for 4 hours, induced the expected rise in the serum LH levels, but serum FSH levels remained low and only at one point reached 0.9 IU/1 (normal adult male basal range 0.9–10.3 IU/1). The patient received LHRH, 100 μg/day, for three days. A second LHRH infusion, 0.2 μg/minute for 4 hours, induced a normal rise in both the serum LH and FSH titers. The serum sex steroid binding globulin level was 10.3 ng DHT bound/ml (normal adult male level 8.0 ± 0.3 ng DHT bound/ml). Presence of circulating autoantibodies to the serum FSH was excluded by determining the binding of [125I] FSH with the patient's serum and comparing it with sera obtained from two normal male adult volunteers. Pituitary function tests were otherwise intact. Presence of a pituitary tumor was excluded by computerized axial tomography and x‐ray studies of the pituitary fossa and normal visual fields. Clinically, the patient demonstrated cryptorchidism, hypospadias, surgically repaired omphalocele, and bilateral hearing loss. Family history for such disorders was negative. Although the initial response of serum FSH in our patient to LHRH stimulation was abnormal, “priming” the patient with LHRH prior to another infusion normalized the response. These data support the hypothesis that in this patient, the pituitary was potentially capable of normal FSH secretion despite undetectable basal levels.
Clinical Experience with An Artificial Spermatocele
Authors: MARMAR JOEL L. , DeBENEDICTIS THOMAS J. , PRAISS DONALD E.
Published: December 2015

Artificial spermatoceles were implanted into three patients with congenital absence of the vas. In each case, the testicular biopsy demonstrated normal spermatogenesis, and the dilated epididymal tubule was packed with spermatozoa. The ciliated epididymal mucosa appeared normal despite the tubular dilatation. The spermatoceles were constructed of expanded polytetrafluoroethylene, and they were microsurgically implanted over the cut end of the epididymis. The grafts were aspirated monthly for up to six months, and the aspirates containing spermatozoa were used for artifical insemination. Spermatozoa were consistently retrieved from each patient, but no pregnancies have resulted. The most obvious finding was that the spermatozoa lacked motility. In the discussion, other problems related to artificial spermatoceles are reviewed, including epididymal development and sperm maturation, aspiration techniques, and sperm storage.
Squash Preparation Studies of Germ Cells in Human Fetal Testes
Authors: SUN ERIC L. , GONDOS BERNARD
Published: December 2015

Testes from human fetuses 21 to 41 weeks of gestation were investigated using a modified squash technique. At all of the gestational ages examined, 90 to 95% of the germ cells were in interphase. Preleptotene germ cells, which exhibited densely staining condensed clumps of chromosomes, were found in all samples studied and constituted 3 to 9% of the germ cells observed. In appearance they resembled preleptotene figures seen in the fetal ovary. Occasionally, germ cells containing slender chromosomes with a beaded appearance, but without prominent condensation, were encountered. These cells were interpreted as preleptotene germ cells in the early stages of degeneration. Germ cells in other meiotic stages were not observed in this study.
Protein Secretion by the Rat Epididymis Can Be Selectively Modified In Vitro by Local Anesthetics, Glucose Deprivation, Dinitrophenol, Ouabain, and Ionophores
Authors: BROOKS DAVID E.
Published: December 2015

Protein secretion by the caput epididymidis has been examined in vitro using radioactive methionine as a precursor for protein synthesis. Newly synthesized and secreted proteins were separated by gel electrophoresis and visualized by fluorography. Local anesthetics such as procaine had the ability to reduce the secretion of some, but not all, proteins. Selective inhibition of secretion of the same proteins occurred when either dihydrocytochalasin B, monensin, ouabain, or dinitrophenol was added to the medium, or when the concentration of glucose was reduced below 1 mM. Calcium ionophore also selectively modified protein secretion, but the proteins affected were different from those influenced by local anesthetics. Other agents tested (eg, adrenergic and cholinergic agonists and antagonists, sodium pentobarbitone, antipsychotic drugs, cyclic AMP, colchicine) did not selectively modify protein secretion, even though overall protein synthesis and secretion was reduced in some instances. Procaine and dihydrocytochalasin B also reduced glucose utilization by epididymal tissue and it is suggested that these agents may reduce protein secretion by limiting the supply of energy for the exocytotic process. This conclusion is supported by the fact that dinitrophenol, an uncoupler of oxidative phosphorylation, caused a similar alteration in protein secretion. The possibility that a restricted energy supply modifies protein secretion primarily by creating a disturbed intracellular Na/K balance is suggested by the observation that the monovalent ionophore, monensin, and the Na/K ATPase inhibitor, ouabain, were both able to duplicate the effects of the local anesthetics.
Lectin‐binding Pattern of Bull Testis and Epididymis
Authors: ARYA MANJULA , VANHA‐PERTTULA TAPANI
Published: December 2015

Seven rhodamine‐conjugated lectins (PNA, RCA I, SBA, Con A, WGA, UEA I, DBA) were used to study the distribution of glycoproteins in the testis and epididymis of immature, juvenile, and adult bulls. A marked change was found in the staining pattern of the lectins in the seminiferous tubules during acrosomal development, and the Sertoli cells seemed to have a cyclic affinity for some of the lectins. The distribution of lectin staining in six regions of the bull epididymis showed some typical differences that were associated with the secretory and absorptive functions of the organ. Region 1 was characterized by strong surface and villous staining and a patchy reaction in the principal cells. Regions 2 and 3 showed a strongly reactive apical Golgi zone and secretory material. In regions 4 and 5, the Golgi zone was subapical but strongly reactive with most lectins, while in region 6 a weakly reactive apical Golgi zone was found. During sexual maturation, an increasing number of basal cells with a strong affinity for some lectins was found at the periphery of the epithelium in regions 2 to 6. These regions also had lectin‐stained material along the basal border of the principal cells. These findings suggest that the basal cells may be active in the digestion of absorbed material and that they derive from the principal cells, which may be active in transporting absorbed material to them. The staining pattern of the spermatozoa changed during their transit through the epididymis. The degenerating cells in the testis and epididymal tubules also showed an altered affinity for the lectins.
Pituitary‐Gonadal Function in Adult Male Rats Subjected to Chronic Water Restriction
Authors: ARMARIO ANTONIO , CAMPMANY LLUIS , LOPEZ‐CALDERON ASUNCION
Published: December 2015

The effect of water restriction on the pituitary‐gonadal axis has been studied in adult male rats. Water restriction did not modify FSH, LH and testosterone levels. However, both LH and testosterone responses to acute noise stress were impaired by water restriction. It was unlikely that the inhibition of the pituitary‐gonadal response to stress was due to an alteration of the circadian pattern of LH since no evidence for such a daily rhythm was found in either of the two experimental groups. The effects of water restriction on the pituitary‐gonadal axis appear to be at least partially a consequence of the resulting reduction in food intake, so that the pituitary‐gonadal response to stress would be a more sensitive index of abnormalities induced by protein‐calorie deficit than basal concentrations of LH, FSH, or T.
A Microperfusion Chamber for Study of Mammalian Spermatozoa
Authors: BURKMNA LANI JOHNSON
Published: December 2015

The design of a microperfusion chamber is presented for use with spermatozoa or other cell suspensions. This chamber allows perfusion of a small number of spermatozoa during simultaneous observation of cell behavior at the microscope. The chamber is made from a flat glass capillary tube that is fitted at both ends with a filter unit containing Millipore filter discs. The entire assembly is designed to fit the stage of an inverted microscope. A population containing as few as several hundred sperm cells may be observed in the chamber during successive changes of the suspending medium as controlled by a perfusion pump. Several experiments are presented demonstrating sperm survival in the sealed chamber and the response of rabbit and human sperm motility after the washing process. For these manipulations, the percentage of motile cells, linear swimming speed and incidence of hyperactivated motility are reported. Simple incubation in the chamber for 1 hour was not deleterious to the motility of rabbit spermatozoa. Human seminal spermatozoa showed no decline in vigorous motility after the washing procedure. Compared with in vitro capacitated spermatozoa, however, washing of rabbit seminal spermatozoa showed a variable response. Finally, partially capacitated human spermatozoa were examined for any alteration of motility during chamber incubation with a subsequent wash. When small numbers of spermatozoa or other cell types must be manipulated, the methodology can be effectively substituted for the standard washing procedure that uses repeated centrifugation and resuspension.
Effects of Cocaine Hydrochloride on Reproductive Function and Sexual Behavior of Male Rats and on the Behavior of Their Offspring
Authors: ABEL E. L. , MOORE C. , WASELEWSKY D. , ZAJAC C. , RUSSELL L. D.
Published: December 2015

Cocaine hydrochloride (30, 15, or 0 mg/kg) was administered daily subcutaneously to male rats (or a minimum of 72 days. Animals receiving the 15‐mg/kg and 0‐mg/kg doses were pair‐fed with animals receiving the higher dose. A fourth group served as a nontreated ad libitum‐fed control to assess the role of cocaine‐associated decreases in food and water intake. Administration of cocaine resulted in dose‐related decreases in body weights, increases in locomotor activity, and decreases in estradiol levels. The high dose of cocaine was also associated with an increase in the percentage of spermatozoa with heads separated from tails. Cocaine did not affect sexual behavior, relative weights of the testis or accessory organs, histology of the testis, number of implantations, resorptions, fetal or newborn weight of offspring, or offspring weight at 21 days of age but did result in hyperactivity and increased perseverance in a T maze.
A Simple, Clinical Assay to Evaluate The Acrosin Activity of Human Spermatozoa
Authors: KENNEDY W.P. , KAMINSKI J.M. , VAN DER VEN H.H. , JEYENDRAN R.S. , REID D.S. , BLACKWELL J. , BIELFELD P. , ZANEVELD L.J.D.
Published: December 2015

Acrosin, a sperm‐specific arosomal proteinase, has an essential role in the fertilization process. Low levels of acrosin appear to be associated with subfertility and infertility, and the acrosin activity of spermatozoa may potentially be a useful indicator of semen quality. The standard acrosin tests employed by research laboratories are too complicated and/or time consuming for clinical use; therefore, a simple assay has been developed to assess total acrosin activity (acrosin and activatable proacrosin). To perform the test, liquefied semen is centrifuged over Ficoll, the washed sperm pellet is suspended in a detergent (Triton X‐100)‐substrate (N‐α‐benzoyl‐DL‐arginine p‐nitroanilide) buffer, pH. 8.0, and the amidase activity is determined spectrophotometrically after a 3‐hour incubation period. Amidase activity can be inhibited with benzamidine, indicating that the activity is primarily or entirely due to acrosin. The absence of detergent in the incubation medium results in greatly reduced activity. The assay is repeatable, linear with increasing sperm concentration, sensitive to a lower limit of 2 × 106 spermatozoa, and the results correspond to those obtained with a standard acrosin extraction and assay technique. Storage of ejaculates at 3 to 6 C or at 22 to 24 C for 24 hours does not affect the acrosin activity significantly but much higher temperatures can cause a loss of activity. Freezing ejaculates results in a large decrease in sperm acrosin activity. Leukocytes show minimal activity in the assay. Sperm populations prepared by a swim‐up procedure average approximately a 2‐fold higher acrosin activity than the original ejaculates. Preliminary experiments indicate that the average sperm acrosin activity of ejaculates whose spermatozoa successfully fertilize human eggs in vitro is significantly higher than those that do not fertilize eggs.
Structure and Control of a Cell‐Cell Adhesion Complex Associated With Spermiation in Rat Seminiferous Epithelium
Authors: CHAPIN ROBERT E. , WINE ROBERT N. , HARRIS MARTHA W. , BORCHERS CRISTOPH H. , HASEMAN JOSEPH K.
Published: December 2015

ABSTRACT: Spermiation, the release of late spermatids from the Sertoli cell, is disrupted by a number of toxicants. Control of the spermiation process, and the proteins that interact to adhere mature spermatids to Sertoli cells, is poorly understood. In these studies we used immunohistochemistry, coimmunoprecipitation/Western blotting, and mass spectrometry to refine an earlier model of sperm adhesion proposed by our laboratory. We have identified specific proteins linked together as part of a multiprotein complex, as well as several additional proteins (cortactin, ERK1/2, and 14‐3‐3 ζ) that may be functioning in both structural and signal transduction roles. The current and prior data suggest that protein phosphorylation is central to the control of spermiation. We also present and characterize an in vitro tubule culture system that allowed functional testing of the spermiation model by pharmacologic manipulation, and yielded data consistent with the importance of protein phosphorylation in spermiation.
Osmotic Tolerance of Equine Spermatozoa and the Effects of Soluble Cryoprotectants on Equine Sperm Motility, Viability, and Mitochondrial Membrane Potential
Authors: BALL BARRY A. , VO ANTHONY
Published: December 2015

ABSTRACT: Osmotic stress attributed to differences in the relative permeability of cryoprotectants, such as glycerol and water, appears to be an important factor in cryodamage. The objective of this study was to characterize the osmotic tolerance of equine spermatozoa, and to evaluate the effects of addition and removal of cryoprotectants from equine spermatozoa on their motility, and membrane and acrosomal integrity, as well as their mitochondrial membrane potential. Equine spermatozoa had a limited osmotic tolerance to anisosmotic conditions. Although the addition of increasing concentrations of glycerol decreased the motility and viability of equine spermatozoa, the rapid removal of glycerol by dilution in isosmotic media resulted in an even greater decline in motility and viability compared with spermatozoa maintained under anisosmotic conditions. Likewise, the addition and rapid removal of 1.0 M glycerol, ethylene glycol, dimethylsulfoxide, or propylene glycol resulted in a significant decline in sperm motility and viability. Among these cryoprotectants, ethylene glycol had the least detrimental effect on either viability or motility of spermatozoa following the rapid addition and removal of these cryoprotectants. These data demonstrate that equine spermatozoa have a limited osmotic tolerance compared with published reports for mouse or human spermatozoa, and appear to be more similar to boar spermatozoa in their osmotic tolerance. Of the 4 cryoprotectants evaluated in equine spermatozoa, the addition and removal of glycerol resulted in a more marked osmotic stress as indicated by alterations in motility, viability, and acrosomal integrity. These data suggest that alternative cryoprotectants should be considered for cryopreservation of equine spermatozoa in order to reduce osmotic stress associated with the addition of these agents during semen freezing.
Sperm Mitochondrial Mutations as a Cause of Low Sperm Motility
Authors: Thangaraj Kumarasamy , Joshi Manjunath B. , Reddy Alla G. , Rasalkar Avinash A. , Singh Lalji
Published: December 2015

ABSTRACT: We report the unique case of a 28‐year‐old man who, in spite of having a varicocele and a sperm concentration of 5 million/mL, of which 10% were motile and 20% had normal forms (oligoasthenoteratozoospermia [OAT]), was fertile. This was confirmed by paternity testing using 16 autosomal and 6 Y‐chromosomal short tandem repeat (STR) loci. An analysis of mitochondrial genes that included cytochrome oxidase I (COI), cytochrome oxidase II (COII), adenosine triphosphate synthase6 (ATPase6), ATPase8, transfer ribonucleic acid (tRNA) serine I, tRNA lysine, and NADH dehydrogenase3 (ND3) revealed, for the first time, 9 missense and 27 silent mutations in the sperm's mitochondrial DNA (mtDNA) but not in the DNA from the blood cells. There was a 2‐nucleotide deletion in the mitochondrial COII genes, introducing a stop codon, which might be responsible for low sperm motility.
Concentration of Glutathione and Expression of Glutathione Peroxidases 1 and 4 in Fresh Sperm Provide a Forecast of the Outcome of Cryopreservation of Human Spermatozoa
Authors: Meseguer M. , Garrido N. , Simón C. , Pellicer A. , Remohí J.
Published: December 2015

ABSTRACT: Oxidative stress imbalance potentially leads to damage of the structure of the cell and macromolecules such as plasma membrane components, proteins, and DNA. The plasma membrane of the sperm cell, which has high levels of polyunsaturated fatty acids, renders it particularly sensitive to free radical—mediated attacks. The freezing and subsequent thawing of sperm is a physically stressful process carried out during routine procedures in assisted reproduction techniques, which results in a highly variable and unpredictable reduction in the number of motile sperm cells. Subsequently, oxidative status can positively or negatively affect the motility, viability, and fertilizing capacity of thawed sperm. These effects are counteracted by various oxidative defense enzymes and anti‐oxidants such as glutathione peroxidase isoforms GPx1 and GPx4, glutathione reductase (GR), and cellular glutathione (reduced) (GSH). In this way, oxidative status could represent a predictive marker of sperm quality following the freeze‐thaw process. This study was based on 56 human sperm samples. We observed direct positive and negative relationships between the postthaw motile sperm recovery rate and GPx1 and GPx4 expression and activity, on the one hand, and GSH concentrations, on the other. No correlation was found between this recovery rate and GR or basic semen parameters. Predictive values clearly demonstrate that, among the molecules analyzed, the most accurate diagnoses result when analyses are conducted for GPx1 and GPx1 messenger RNA expression, GPx1 and GPx4 enzymatic activity, and GSH concentration. In conclusion, a reserve of glutathione, together with GPx expression, is necessary to eliminate free radicals using GSH or a like structural protein and seems to be essential for a good postthaw recovery. These molecules can be employed as indicators of postthaw sperm quality.
Electroejaculation With a Foley Catheter in the Bladder
Authors: Hovav Yedidya , Sibirsky Ohn , Davarashvili Anna , Yaffe Haim
Published: December 2015

ABSTRACT: Electroejaculation has been successfully used for sperm procurement in anejaculatory men desiring fertility. The electroejaculation procedure begins with complete catheterization of the bladder and instillation of an insemination medium into the bladder as a buffer. This step can minimize possible detrimental effects of urine on any retrograde ejaculate. The catheter is then removed. After the collection of the antegrade ejaculate, the bladder is catheterized again. Our objective was to evaluate the possibility of performing electroejaculation while the Foley catheter is instilled in the bladder. Eleven men with anejaculation underwent 22 procedures of rectal probe electroejaculation. Each patient underwent electroejaculation twice, once without the catheter instilled in the bladder (standard method) and once with it. The 2 methods, with and without the catheter, showed no significant differences in volume, concentration, motility, count, and total motility of the antegrade ejaculate. In retrograde ejaculate, there were no significant differences in the count, motility, and total motility. In addition, there was no difference in the total count and the total motility of both fractions in the 2 methods. In this study, we show that ejaculation can be achieved while the Foley catheter is instilled in the urethra without any detrimental effect on the sperm. Therefore, we recommend not removing the Foley catheter while performing electroejaculation.
Stereological Quantification of Nerve Fibers Immunoreactive to PGP 9.5, NPY, and VIP in Rat Prostate During Postnatal Development
Authors: Rodríguez Rosario , Pozuelo José M. , Martín Rocío , Arriazu Riánsares , Santamaría Luis
Published: December 2015

ABSTRACT: This work was undertaken to study prostate innervation during the postnatal development of rats. It deals with the quantification of nervous fibers throughout all the regions of the rat prostate during the postnatal development using a general marker for nervous tissue, protein gene product 9.5, and 2 neuropeptides (NPY and VIP). Forty male Wistar rats (prepubertals, pubertals, young, and aged adults) were studied for immunohistochemistry of protein gene product (PGP 9.5), neuropeptide Y (NPY), and vasoactive intestinal polypeptide (VIP). They were also evaluated for length density of nerve fibers (LV PGP 9.5, LV NPY, LV VIP). Nerve fibers immunoreactive to the 3 antigens studied were detected in all the groups and in all the prostate zones. Periductal LV NPY evidenced a significant increase in the pubertal group, maintained throughout adult life. Periductal LV VIP showed a significant increase in young adults. The length densities of VIP and NPY fibers were significantly higher in periductal and ampular locations in comparison with dorsal and ventral sites. It can be concluded that the relative amount of nerve fibers in rat prostate, detected by PGP 9.5, does not change during postnatal development. There were significant changes in NPY and VIP fibers, showing an increase in periurethral ducts at puberty. The abundance of peptidergic innervation around the excretory ducts is related to their contractility. The development of innervation of periurethral ducts is regulated by androgens.
Stage‐ and Cell‐Specific Expression of Soluble Guanylyl Cyclase Alpha and Beta Subunits, cGMP‐Dependent Protein Kinase I Alpha and Beta, and Cyclic Nucleotide‐Gated Channel Subunit 1 in the Rat Testis
Authors: Shi Fangxiong , Wang Tian
Published: December 2015

ABSTRACT: Several studies suggest that nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) modulate testicular function. In this study, we examined the expression of cGMP‐dependent protein kinase G‐I (PKG‐I), and cyclic nucleotide‐gated channel 1 (CNG‐1), 2 known mediators of cGMP action, and the expression of soluble guanylyl cyclase (sGC) subunits in the rat testis. Immunohistochemical analysis revealed that the alpha subunit of sGC was expressed in the blood vessels and Leydig cells of adult rat testes. In addition, the sGC alpha subunit was observed in the acrosomal structures of spermatids undergoing the middle and later stages of spermiogenesis, but not in mature spermatozoa. Similar localization and expression patterns were seen for the sGC beta subunit, indicating coexpression of the sGC subunits. PKG‐I was expressed in blood vessels and in the acrosomal region of spermatids during the early and middle stages of spermiogenesis but was not observed in Leydig cells or in mature spermatozoa. In contrast to sGC and PKG‐I, CNG‐1 was expressed only in cytoplasm and the residual bodies of late‐stage (17–19) spermatids, with no staining observed in blood vessels and Leydig cells. These results demonstrate that sGC, PKG‐I, and CNG‐1 are expressed in a stage‐ and cell‐specific manner in the rat testis. The distinct temporal patterns of expression of these components of cGMP signaling pathways suggest different physiological roles for sGC, PKG‐I, and CNG‐1 in spermiogenesis and steroidogenesis.