Simon Maddocks

Intrabursal Injection of Clodronate Liposomes Causes Macrophage Depletion and Inhibits Ovulation in the Mouse Ovary

Abstract To investigate the role of the ovarian macrophage population in ovulation, we examined the effect of depleting this population using liposome-encapsulated clodronate. Clodronate liposomes, saline liposomes, or saline alone was injected under the ovarian bursa in gonadotropin-primed adult mice, either 84 h (Day −3) or 36 h (Day −1) before ovulation. Ovulation rates were determined by counting the number of oocytes released. The numbers of graafian follicles and corpora lutea were also counted immediately before and after ovulation. Macrophage distribution within the theca and stroma of preovulatory ovaries was examined by immunohistochemistry with specific monoclonal antibodies to the macrophage antigens macrosialin, major histocompatability complex class II (Ia), and F4/80. Injection of clodronate liposomes on Day −1 did not affect ovulation rates, whereas administration on Day −3 caused a significant reduction in ovulation rate (mean oocytes ovulated = 5.25 ± 0.6 from clodronate liposome-treated ovaries and 9.13 ± 0.9 from saline-treated ovaries, respectively, P < 0.05). The numbers of macrosialin-positive macrophages present in the theca at ovulation were reduced by treatment with clodronate liposomes on Day −1, and treatment on Day −3 reduced the numbers of Ia-positive and macrosialin-positive macrophages present in the theca. When the subsequent ovarian cycles were examined by vaginal smearing, the metestrous-2/diestrous stage was found to be extended in clodronate liposome-treated animals (7.5 ± 1.3 days vs. 3.4 ± 0.4 days for saline liposome-treated animals, P < 0.05). These results suggest that thecal macrophages may be involved in the regulation of follicular growth and rupture, as well as being important for the normal progression of the estrous cycle.

Recent evidence for immune privilege in the testis.

In the last 20 years, it has been shown that while first-set intra-testicular grafts rarely induce systemic immunity, second-set intra-testicular grafts are usually rejected, if a pre-existing immunity has been generated by first-set skin grafts. These observations suggest that while the efferent limb of the pre-sensitized immune response is operative in the testis, the immune system can not be activated against antigens present only in this site. Various theories have been advanced to explain this phenomenon. The most likely explanation at present seems to be that the testis contains specific immunosuppressive factors that inhibit lymphocyte activation in this site.

Testis physiology relevant to immunoregulation

Intra-testicular transplants are placed in rodents into the large lymphatic sinusoids of the interstitial tissue of the testis. These sinusoids are filled with a protein-rich extracellular fluid that supplies all the requirements of the grafts until vascularization takes place. The testicular microvascular endothelium regulates transport of T lymphocytes and immunoglobulin G to the testis and may thus contribute to regulation of the immune system in this organ. Differences in the organization of the lymphatic drainage exist between species, but in every studied species lymphatic drainage from the testis leads to lymph nodes.

Wireless RF communication in biomedical applications

This paper focuses on wireless transcutaneous RF communication in biomedical applications. It discusses current technology, restrictions and applications and also illustrates possible future developments. It focuses on the application in biotelemetry where the system consists of a transmitter and a receiver with a transmission link in between. The transmitted information can either be a biopotential or a nonelectric value like arterial pressure, respiration, body temperature or pH value. In this paper the use of radio-frequency (RF) communication and identification for those applications is described. Basically, radio-frequency identification or RFID is a technology that is analogous to the working principle of magnetic barcode systems. Unlike magnetic barcodes, passive RFID can be used in extreme climatic conditions—also the tags do not need to be within close proximity of the reader. Our proposed solution is to exploit an exciting new development in making circuits on polymers without the need for battery power. This solution exploits the principle of a surface acoustic wave (SAW) device on a polymer substrate. The SAW device is a set of interdigitated conducting fingers on the polymer substrate. If an appropriate RF signal is sent to the device, the fingers act as microantennas that pick up the signal, and this energy is then converted into acoustic waves that travel across the surface of the polymer substrate. Being a flexible polymer, the acoustic waves cause stresses that can either contract or stretch the material. In our case we mainly focus on an RF controllable microvalve that could ultimately be used for fertility control.

Regulation of the testis

The testicular cells are regulated by factors produced locally in the testis. These factors include peptide growth factors, pro-opiomelanocortin derivatives, neuropeptides and steroids. Several agents able to affect steroido- and spermatogenesis can also affect leukocytes and many of the testis-regulating factors are produced by immune cells, suggesting that testicular cells and leukocytes may interact. In the present article, the effects of various testicular cell and leukocyte produced factors on steroido- and spermatogenesis are reviewed. The possibility that leukocytes may produce substances able to affect the testicular functions suggests that inhibition of immune system activation in the testis may be important also for reasons other than protection of autoantigenic germ cells from an autoimmune attack.

Trade-Offs for Wireless Transcutaneous RF Communication in Biotelemetric Applications

The application of biotelemetry in the case of a RF controllable microvalve is discussed. Biotelemetry implies the contactless measurement of different electrical and nonelectrical parameters measured on human or animal subjects. A biotelemetry system consists of a transmitter and a receiver with a transmission link in-between. Transmitted information can be a biopotential or a nonelectric value like arterial pressure, respiration, body temperature or pH value. Transducers convert nonelectrical values into electrical signals. Radio frequency (RF) telemetry allows a patient greater mobility. Above all, the application of wireless communication becomes more and more popular in microinvasive surgery. Battery powered implants are most commonly used, but batteries must be changed after a period of time. To avoid this, wireless transcutaneous radio frequency (RF) communication is proposed for the powering and control of medical implants.