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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ejor.2007.12.008 Byline: Igor Bykadorov (a), Andrea Ellero (b), Elena Moretti (b), Silvia Vianello (c) Keywords: Wholesale price; Sales motivation; Optimal control Abstract: The main goal of this paper is to model the effects of wholesale price control on manufacturer's profit, taking explicitly into account the retailer's sales motivation and performance. We consider a stylized distribution channel where a manufacturer sells a single kind of good to a single retailer. Wholesale price discounts are assumed to increase the retailer's motivation thus improving sales. We study the manufacturer's profit maximization problem as an optimal control model where the manufacturer's control is the discount on wholesale price and retailer's motivation is one of the state variables. In particular in the paper we prove that an increasing discount policy is optimal for the manufacturer when the retailer is not efficient while efficient retailers may require to decrease the trade discounts at the end of the selling period. Computational experiments point out how the discount on wholesale price passed by the retailer to the market (pass-through) influences the optimal profit of the manufacturer. Author Affiliation: (a) Sobolev Institute of Mathematics, Siberian Branch of the Russian Academy of Sciences, 4 Acad. Koptyug Avenue, 630090 Novosibirsk, Russia (b) Department of Applied Mathematics, University Ca' Foscari of Venice, Dorsoduro 3825/E, 30123 Venezia, Italy (c) Department of Business and Management Studies, University Ca' Foscari of Venice, Cannaregio 873, 30121 Venezia, Italy Article History: Received 23 January 2007; Accepted 6 December 2007

Objective: To investigate the relationship between chronic infections detected in serum and semen quality. The pathogen burden is a concept consisting in the observation that, in patients with heart disease, damaging effects of the coronary arteries increase concomitantly with the number of agents responsible for chronic infections to which patients mounted a serological response. Previous observations that Helicobacter pylori infection may reduce the semen quality prompted us to perform the present study.Methods: Blood and semen samples were collected from 73 selected men, enrolled from January 2014 to January 2015. Semen characteristics were evaluated by light and transmission electron microscopy. Transmission electron microscopy data were quantified with a mathematical formula providing numerical scores, such as fertility index (FI, number of sperm free from ultrastructural defects) and the percentages of sperm apoptosis, immaturity, and necrosis. Serum samples were examined by enzyme-linked immunosorbent assay for the presence of immunoglobulin G to the most common agents of chronic infections such as H. pylori (HP), Mycoplasma pneumoniae (MP), Chlamydophila pneumoniae (CP), Epstein-Barr virus (EBV), herpes simplex virus 1 (HSV-1), and cytomegalovirus (CMV).Results: The prevalence of infections was as follows: HP 43.8%, CP 46.6%, MP 72.6%, EBV 95.9%, HSV-1 74.0%, and CMV 46.6%. Concomitantly with the increased number of pathogens against which the patients mounted a significant antibody response, sperm concentration (P <.05), sperm motility (P <.001), and fertility index (P <.001) were significantly reduced and the percentage of necrotic sperm was increased (P <.01).Conclusion: The higher the number of pathogens stimulating an immunoglobulin G systemic response, the lower was the semen quality. [ABSTRACT FROM AUTHOR]

A strategy to circumvent the poor polyphenols bioavailability is to load these compounds into liposomes. We evaluated the in vitro effects of quercetin (Q) and Q-loaded liposomes (QLL, 30, 50, 100 μM) on motility, viability and chromatin integrity of swim-up selected human sperm. Antioxidant power was assayed against tert-butylhydroperoxide induced lipid peroxidation (LPO) using C11-BODIPY581/591 fluorescent probe and transmission electron microscopy. QLL showed decreased toxicity for sperm motility and viability and increased DNA damage compared to Q. The percentage of sperm with fluorescence, marker of LPO, was decreased in samples incubated with Q vs QLL (P < 0.001). The ultrastructure of acrosomes and membranes was preserved with Q 30/100 μM, whereas QLL did not prevent membrane injury. Q alone appeared more effective than Q incorporated into liposomes; however liposomes could be considered as carriers that may convey different compounds inside sperm; they may therefore represent a field of research rich of many applications. [ABSTRACT FROM AUTHOR]

Objective To explore the relationships between seminal interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) with semen parameters, sperm apoptosis, and necrosis in subjects infected by Helicobacter pylori (HP) expressing and not expressing CagA. Methods In 109 selected patients, HP infection and seminal levels of IL-6 and TNF-α were determined using enzyme-linked immunosorbent assays. Western blotting was used to detect antibodies to CagA. Semen parameters were determined following World Health Organization guidelines and sperm apoptosis and necrosis by annexin V and propidium iodide assay. Results Twenty-eight subjects were infected by HP (HP+); among them, 12 were CagA seropositive (CagA+) and 16 were negative (CagA−). Eighty-one men were HP seronegative (HP−). Semen TNF-α and IL-6 concentrations were increased in HP+ vs HP− groups (TNF-α: 41 pg/mL vs 27 pg/mL; IL-6: 11 pg/mL vs 5 pg/mL; P <.01). In comparison to the HP− group, CagA+ group showed reduced sperm motility (24% vs 32% motile sperm; P <.05), enhanced necrosis (33.5% vs 21% necrotic sperm; P <.05), and increased cytokines levels (TNF-α: 46 pg/mL vs 27 pg/mL; P <.01; IL-6: 17.5 pg/mL vs 5 pg/mL; P <.01). Sperm motility of CagA+ group was lower vs CagA− group (24% vs 36.5% motile sperm; P <.05). Both IL-6 and TNF-α levels positively correlated with the percentage of necrotic sperm ( P <.001). Conclusion CagA+ HP infection increases semen levels of inflammatory cytokines, which may reduce sperm motility and determine sperm damage and contribute to reduce the reproductive potential in men. [ABSTRACT FROM AUTHOR]

Objective To explore the relationships between resistin, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) and semen parameters, sperm apoptosis, and necrosis in infertile patients and in control subjects with unknown reproductive potential with/without smoking habits, leukocytospermia, and varicocele. Design Prospective study. Setting Sperm laboratory. Patient(s) A total of 110 selected men. Intervention(s) Family history, clinical/physical examination, ELISA determination (resistin, IL-6, TNF-α), semen analysis, annexin V/propidium iodide assay. Main Outcome Measure(s) Relationships among resistin, IL-6, and TNF-α and semen parameters in the presence of smoking habits, varicocele, leukocytospermia, and in infertile subjects. Result(s) Resistin level was higher in semen than in serum. Resistin semen levels showed negative correlations with sperm motility and positive correlations with apoptotic, necrotic sperm and TNF-α and IL-6 levels. Resistin, TNF-α, and IL-6 levels were higher in smokers compared with nonsmokers and in cases with leukocytospermia, in which an increase in necrotic sperm and a decrease in the number of sperm with normal morphology and motility were observed. Cytokine levels were significantly higher in infertile patients compared with control subjects with unknown reproductive potential. A total of 74.5% of infertile patients showed leukocytospermia. Conclusion(s) Semen resistin correlated with IL-6, TNF-α, and sperm quality; in cases of leukocytospermia and smoking habits, resistin concentrations were increased, suggesting that resistin may play a regulatory role in inflammation of the male reproductive system. [ABSTRACT FROM AUTHOR]

Abstract: Submicroscopic 6p25 deletion is now recognized as a clinically identifiable syndrome, characterized by intellectual disability, language impairment, hearing deficit, craniofacial, ophthalmologic, cardiac, and varying central nervous system anomalies. We report on two dyzogotic twins with a maternal segregating hemizygous interstitial deletion on chromosome 6p25.1, spanning 0.9 kb; the smallest ever reported. Both had dysmorphic features (prominence of the metopic suture, synophrys, hypertelorism, down-slanting palpebral fissures, tented mouth), and a distinct brain MRI, showing a focal significant increase of the right peri-frontal subarachnoid space, with shallow sulci and a mild anomaly of the gyral pattern. Such brain anomaly has never been reported in association with del 6p25. Both propositi had a borderline-mild intellectual disability, speech and language difficulties, and behavior abnormalities. Their mother, formally tested, had a borderline cognitive impairment. Although none of the genes mapping to the deleted region are apparently related to the phenotype, LYRM4 resulted down-regulated in the cerebellar cortex of schizophrenia patients compared with controls, and Lyrm4 was down-regulated in the prefrontal cortex of mice with microdeletions in the locus syntenic to human 22q11.2 patients affected by schizophrenia. These data are in agreement with the emerging concept that similar CNVs are pathogenic in patients affected by distinct neurological diseases, and that these loci are more general risk factors for different disorders. The resemblance of our patients to those with the more extensive 6p25.1p25.3 terminal deletion suggests that the gene/s responsible for the physical phenotype should reside in the 6p25.1 genomic region. [Copyright &y& Elsevier]

Objective: To investigate the occurrence of ghrelin and obestatin in human semen. Design: Prospective study. Setting: University, center for research and therapy of male infertility. Patient(s): 112 consecutively selected men. Intervention(s): Family history, clinical and physical examination, radioimmunoassay for ghrelin and obestatin determinations, semen analysis, annexinV/propidium iodide assay. Main Outcome Measure(s): Ghrelin and obestatin detected in the semen and relationships with semen parameters and conditions influencing semen quality (smoking, varicocele, ex varicocele, leukocytospermia). Result(s): The levels of both peptides in semen were higher versus serum. Linear correlations between ghrelin and obestatin levels in serum and in semen were observed. Serum ghrelin levels were negatively correlated with the men’s ages. Semen obestatin levels were positively correlated with sperm concentration and motility. Obestatin levels were decreased in the semen of smokers and in the presence of leukocytospermia. Conclusion(s): This is the first study on the presence of obestatin in human semen and its relationship with sperm concentration and motility, suggesting a possible role of the peptide in controlling cell proliferation and survival. Further investigations are required to explore the exact role of obestatin and ghrelin in human semen. [ABSTRACT FROM AUTHOR]

We have discovered, by immunocytochemistry and immunoelectronmicroscopy, that humanin (HN) is expressed in human ejaculated sperm and testis. In sperm, the HN immunolabeling pattern depends on sperm morphology; in particular, HN is mainly localized in the midpiece of sperm in semen samples with normal morphology and in cytoplasmic residues and entire tail in those with abnormal morphology. We also found HN in the cytoplasm and nucleus of spermatocytes and spermatids and in experimentally uncoiled chromatin of mature ejaculated sperm. Because it has been established that HN has antiapoptotic properties, it is reasonably hypothesized that HN may play an important role in preventing apoptosis in human sperm and testis. Thus, the examination of the HN localization in normal and abnormal sperm could be proposed as an auxiliary test to better define sperm quality. [ABSTRACT FROM AUTHOR]

• The relevance of isoprostanoids in human semen quality was investigated. • F 2 -dihomo-IsoPs was significantly higher in varicocele group respect to fertile men. • F 2 -IsoPs positively correlated with F 2 -dihomo-IsoPs in the whole population. • F 4 -NeuroPs positively correlated with sperm necrosis in idiopathic infertility group. • Isoprostanoid semen levels appear to be associated with male infertility. The aim of this paper was to investigate the relevance of isoprostanoids i.e., F 2 -isoprostanes (F 2 -IsoPs), F 4 -neuroprostanes (F 4 -NeuroPs) and F 2 -dihomo-isoprostanes (F 2 -dihomo-IsoPs) in semen quality. Isoprostanoid levels were detected in semen of fertile and infertile men with varicocele or idiopathic infertility. Semen quality was assessed by light microscopy and transmission electron microscopy; the relationships between isoprostanes and semen parameters were also explored. F 2 -IsoPs levels were significantly different in the varicocele group compared to idiopathic infertile group and fertile men (P < 0.01 and P < 0.001 respectively). Moreover, F 2 -dihomo-IsoP values were significantly higher in varicocele group respect to fertile men (P < 0.05). No significant statistical differences were found regarding F 4 -NeuroP concentrations. In the whole population, F 2 -IsoPs positively correlated with F 2 -dihomo-IsoPs and both isoprostanoids showed a positive correlation with immaturity and a negative correlation with sperm motility. F 2 -IsoP levels were positively correlated with the percentage of immaturity in infertile varicocele groups (P < 0.01) whereas a significant relationship between F 4 -NeuroP values and the percentage of sperm necrosis was shown in idiopathic infertility group (P < 0.01). A significant negative correlation of F 4 -NeuroPs with sperm morphology was detected in infertile varicocele subjects (P < 0.05). This study suggests that isoprostanoid semen levels appear to be associated with male infertility being related to the sperm quality and confirming the important role of fatty acids profiling in human sperm maturation. [ABSTRACT FROM AUTHOR]

Objective: To characterize the association of two systematic sperm defects. Design: Case report. Setting: University, Interdepartmental Centre for Research and Therapy of Male Infertility. Patient(s): Patient 1, 42 years old, and patient 2, 38 years old, both with severe asthenozoospermia. Intervention(s): Family history, physical examination, hormonal analysis, microbial assays, semen analysis, transmission and scanning electron microscopy, immunocytochemistry for tubulin, and fluorescence in situ hybridization (FISH) for chromosomes 18, X, and Y. Main Outcome Measure(s): Admixture of dysplasia of the fibrous sheath (DFS) and head-tail misalignment up to acephalic sperm detected by microscopic methods. Result(s): In both patients, DFS was present in incomplete form and was associated with acephalic sperm and abnormal head-tail attachment. In patient 2, spermatozoa were also affected by necrosis that may cause fragmentation leading to short flagella; submicroscopic examination allowed defining only the origin of these “stumpy” tails. Immunofluorescence confirmed the sperm alterations. FISH revealed an altered frequency of diploidy and disomy in patient 2 and a slight increase in diploidy in patient 1. Conclusion(s): The importance of ultrastructural sperm evaluation for correct identification of sperm pathologies is evident, particularly regarding assisted reproduction technology and genetic risk assessment. [ABSTRACT FROM AUTHOR]

Objective: To characterize a flagellar defect involving 95% of the sperm population from an infertile man. Design: Case report. Setting: Interdepartmental Centre for Research and Therapy of Male Infertility, Siena, Italy. Patient(s): A 42-year-old infertile man with severe asthenozoospermia. Intervention(s): Family history, physical examination, hormonal analysis, microbial assays, semen analysis, transmission electron microscopy (TEM) and scanning electron microscopy (SEM), tubulin distribution investigated by immunocytochemistry, fluorescence in situ hybridization for chromosomes 18, X, and Y. Main Outcome Measure(s): Ultrastructural abnormalities of the flagellum detected by methods listed. Result(s): Ultrastructural analysis revealed, in 95% of sperm cells, the total absence of the axoneme and outer dense fibers at the principal piece level, whereas the midpiece appeared abnormally long. Tubulin localization showed a total disorganization of the axoneme with a network of microtubular structures emerging randomly at any level of the flagellum. Fluorescence in situ hybridization analysis was normal. Conclusion(s): We report a rare sperm tail defect, characterized by abnormal elongation of the midpiece and absence of the axoneme and the outer dense fibers at the principal piece level in 95% of flagella. This defect occurs in the vast majority of the sperm population from a sterile man, and therefore a genetic origin could be hypothesized. [Copyright &y& Elsevier]

Abstract: In the present study, the role of rabbit seminal granules was observed. Their influence on motility, capacitation and acrosome reaction, as well as the presence of apoptosis and the morphology of rabbit sperm, were compared in different conditions. Ejaculated sperm from five mature New Zealand White rabbit bucks during three series of collections were studied, comparing raw semen, Percoll-selected sperm and Percoll-selected sperm plus prostate granules. We observed sperm motility kinetic traits by computer-assisted sperm analyzer (CASA) analysis in each sample. Acrosome status was evaluated by FITC-labeled Pisum sativum Agglutinin staining and chlortetracycline fluorescence assay, phosphatidylserine translocation was determined by AnnexinV/Propidium iodide assay and sperm morphology was studied using transmission electron microscopy (TEM). All traits were observed after 30 min incubation at 37 °C in 5% CO2. Data showed that sperm motility and viability markedly improved in the presence of prostate granules, whereas capacitation, acrosome reaction and phosphatidylserine translocation were lowered. TEM confirmed these results. In conclusion, the role of granules was confirmed in synchronizing sperm capacitation and acrosome reaction with egg availability; indeed, rabbit ovulation occurs only 6 to 10 h after mating. [Copyright &y& Elsevier]

Abstract: Metal compounds have been associated with male reproductive toxicity in vivo. The aim of the present study was to investigate the in vitro effects of 20 metal compounds using rabbit ejaculated spermatozoa as a study model for spermiotoxicity. Five of the metals tested (arsenic, cadmium, chromium, mercury and vanadium) reduced sperm motility and curvilinear velocity. Ultrastructural analyses revealed three types of damage to sperm head membranes in relation to the metal used: acrosome breakage with formation of various sized microvesicles (arsenic, cadmium, mercury and platinum); a large round hole (arsenic, cadmium and chromium), and numerous folds in the acrosome membrane (vanadium). The vanadium compound, followed by chromium and mercury compounds, determined a higher number of damaged spermatozoa. In conclusion, all the studied metal compounds, at levels higher than 1μM, may reduce sperm kinetic characteristics and probably fertilizing capacity by triggering specific morphological damages to the head and/or by inhibiting motility. [Copyright &y& Elsevier]

Objective: To investigate the characteristics of birefringence in human sperm heads and apply polarization microscopy for sperm selection at intracytoplasmic sperm injection (ICSI). Design: Prospective randomized study. Setting: Reproductive Medicine Unit, Società Italiana Studi Medicina della Riproduzione, Bologna, Italy. Patient(s): A total of 112 male patients had birefringent sperm selected for ICSI (study group). The clinical outcome was compared with that obtained in 119 couples who underwent a conventional ICSI cycle (control group). Intervention(s): The proportion of birefringent spermatozoa was evaluated before and after treatment in relation to the sperm sample quality. Embryo development and clinical outcome in the study group were compared with those in the controls. Main Outcome Measure(s): Proportion of birefringent sperm heads, rates of fertilization, cleavage, pregnancy, implantation, and ongoing implantation. Result(s): The proportion of birefringent spermatozoa was significantly higher in normospermic samples when compared with oligoasthenoteratospermic samples with no progressive motility and testicular sperm extraction samples. Although fertilization and cleavage rates did not differ between the study and control groups, in the most severe male factor condition (oligoasthenoteratospermic with no progressive motility and testicular sperm extraction), the rates of clinical pregnancy, ongoing pregnancy, and implantation were significantly higher in the study group versus the controls. Conclusion(s): The analysis of birefringence in the sperm head could represent both a diagnostic tool and a novel method for sperm selection. [Copyright &y& Elsevier]

Objective: To perform fluorescence in situ hybridization (FISH) and molecular analysis in patients with the genetic sperm defect “dysplasia of the fibrous sheath” (DFS). Design: Retrospective study. Setting: Regional Referral Center for Male Infertility, Siena, Italy. Patient(s): Twelve infertile patients with DFS sperm defects. Intervention(s): Family history, lymphocytic karyotype, physical and hormonal assays, semen analysis. Main Outcome Measure(s): The DFS sperm phenotype was defined by light, fluorescent, and electron microscopy. Sperm chromosomal constitution was examined by FISH. Gene deletions were tested by polymerase chain reaction. Result(s): The genetic sperm defect DFS was determined by transmission and scanning electron microscopy. Immunofluorescence staining of A-kinase anchoring protein 4 (AKAP4) showed a moderate and diffuse signal, revealing a disorganized and incompletely assembled fibrous sheath. In 11 of 12 DFS patients, polymerase chain reaction for detecting the presence of partial sequence of AKAP4/AKAP3 binding regions gave positive results. Fluorescence in situ hybridization was performed in decondensed sperm nuclei with probes for chromosomes 18, X, and Y. The mean disomy frequency of chromosome 18 was in the normal range, whereas the mean disomy frequencies of sex chromosomes and diploidies were twice those of controls. Conclusion(s): These results should be considered when DFS sperm are used in assisted reproductive technology, owing to the high risk of transmission of chromosomal unbalance and of DFS sperm defects to male offspring. [Copyright &y& Elsevier]

Objective: To characterize and describe the ontogenesis of a rare flagellar defect affecting the whole sperm population of a sterile man.Design: Case report.Setting: Regional referral center for male infertility in Siena, Italy.Patient(s): A 28-year-old man with severe asthenozoospermia.Intervention(s): Physical and hormonal assays, semen analysis, and testicular biopsy.Main outcome measure(s): Semen samples and testicular biopsies were analyzed by light and transmission electron microscopy; immunocytochemical study with anti-β-tubulin and anti-AKAP 82 antibodies was performed to detect the presence and distribution of proteins.Result(s): Ultrastructural analysis of ejaculated spermatozoa and testicular biopsy revealed absence of the fibrous sheath in the principal-piece region of the tail. Fibrous sheath-like structures were observed in cytoplasmic residues and residual bodies released by spermatids in the seminiferous epithelium. Other anomalies observed were supplementary axonemes and mitochondrial helix elongation. These features were confirmed by immunocytochemical staining.Conclusion(s): This rare sperm tail defect, characterized by absence of the fibrous sheath, presence of supplementary axonemes, and an abnormally elongated midpiece, originates in the seminiferous tubules during spermiogenesis, as detected in testicular biopsy sections. These defects occur in the whole sperm population, and therefore a genetic origin could be suggested. [Copyright &y& Elsevier]

Objective: To characterize a novel flagellar defect involving 98% of sperm tails. Design: Case report. Setting: Interdepartmental Centre for Research and Therapy of Male Infertility, Siena, Italy. Patient(s): A 45-year-old infertile man with severe asthenozoospermia. Intervention(s): Family history, physical examination, hormonal analysis, microbial assays, semen analysis, transmission and scanning electron microscopy, tubulin distribution investigated by immunocytochemistry, fluorescence in situ hybridization (FISH) for chromosomes 9, 16, 18, X, and Y. Main Outcome Measure(s): Flagellar abnormalities detected by microscopical methods. Result(s): An apparent heterogeneity was observed: extremely elongated tails prone to ruptures; coiled tails at different levels with a strongly rolled axoneme or with a curl in the final flagellar segment; and V-shaped, isolated, bent tails. Transmission electron microscopy revealed the presence of normal heads, disorganized flagellar structures, and dynein deficiency. The FISH analysis was normal. Conclusion(s): We report a new sperm defect, characterized by abnormal elongation of the tail, which was prone to ruptures at different levels, concomitant with coiled tails, which were impossible to measure in length. This defect remained constant in different examined ejaculates and applied to the entire sperm population of a sterile man, the son of first-degree cousins, indicating a potential genetic origin. [Copyright &y& Elsevier]