The onset of puberty in colony-housed male and female titi monkeys (Plecturocebus cupreus): Possible effects of oxytocin treatment during peri-adolescent development.

Oxytocin has been used to treat neurodevelopmental conditions in adolescent patients but possible effects on reproductive development have not been well investigated. The effects of daily intra-nasal oxytocin treatment (12-18 months of age) on puberty and fertility were studied in colony-housed, male and female titi monkeys (Plecturocebus cupreus). Body weight, urinary conjugated pregnanes and estrogens (defining cyclicity) in females, and androgens and sperm in urine of in males, were measured from 1 to 3 years of age to detect puberty. Serum testosterone was also measured in males at 13, 23 and 33 months of age and hemi-castration at 3 years of age enabled assessment of testicular morphometry and oxytocin receptor expression. An oxytocin treatment*time interaction suggested a minor, transient suppression in weight gain after treatment ended. Note that females weighed 10% less across all ages. Oxytocin-treated females exhibited early, spurious ovulations but neither regular cyclicity (≈30 months) nor pregnancies were affected by treatment. Oxytocin did not affect the pubertal increase in urinary androgen or the first appearance of sperm, which occurred as early as 15 months of age. Treatment did delay the puberty-associated rise in serum testosterone in males. All males were pubertal by 22 months and all females by 32 months of age. Although no major male or female fertility outcome was observed, oxytocin demonstrated some physiological effects through a delay of testosterone secretion in males, induction of precocious ovulation in females, and a suppression of general weight gain for the months following treatment.

Long-term exposure to intranasal oxytocin in a mouse autism model.

Oxytocin (OT) is a neuropeptide involved in mammalian social behavior. It is currently in clinical trials for the treatment of autism spectrum disorder (ASD). Previous studies in healthy rodents (prairie voles and C57BL/6J mice) have shown that there may be detrimental effects of long-term intranasal administration, raising the questions about safety and efficacy. To investigate the effects of OT on the aspects of ASD phenotype, we conducted the first study of chronic intranasal OT in a well-validated mouse model of autism, the BTBR T+ Itpr3tf/J inbred strain (BTBR), which displays low sociability and high repetitive behaviors. BTBR and C57BL/6J (B6) mice (N=94) were administered 0.8 IU/kg of OT intranasally, daily for 30 days, starting on day 21. We ran a well-characterized set of behavioral tasks relevant to diagnostic and associated symptoms of autism, including juvenile reciprocal social interactions, three-chambered social approach, open-field exploratory activity, repetitive self-grooming and fear-conditioned learning and memory, some during and some post treatment. Intranasal OT did not improve autism-relevant behaviors in BTBR, except for female sniffing in the three-chambered social interaction test. Male saline-treated BTBR mice showed increased interest in a novel mouse, both in chamber time and sniffing time, whereas OT-treated male BTBR mice showed a preference for the novel mouse in sniffing time only. No deleterious effects of OT were detected in either B6 or BTBR mice, except possibly for the lack of a preference for the novel mouse's chamber in OT-treated male BTBR mice. These results highlight the complexity inherent in understanding the effects of OT on behavior. Future investigations of chronic intranasal OT should include a wider dose range and early developmental time points in both healthy rodents and ASD models to affirm the efficacy and safety of OT.

Phase contrast in Simultaneous Topography and Recognition imaging.

The operation of a force microscope in Simultaneous Topography and Recognition (TREC) imaging mode is analyzed by means of numerical simulations. Both topography and recognition signals are analyzed by using a worm-like chain force as the specific interaction between the functionalized tip probe and the sample. The special feedback mechanism in this mode is shown to couple the phase signal to the presence of molecular recognition interactions even in absence of dissipation.

Cigarette smoking and rheumatoid arthritis.

OBJECTIVES: To examine and explore the potential relationships among the following: the incidence/severity of rheumatoid arthritis (RA), the extra-articular manifestations of RA, vascular disease, certain specific malignancies, the p53 tumor suppressor gene, and cigarette smoking. METHODS: The medical literature was reviewed from 1985 to 2001 with the assistance of a MEDLINE search using the key words vascular disease, smoking, protein p53, RA, rheumatoid vasculitis, cancer, and malignancies. A qualitative review was performed after all articles were abstracted and new information summarized. RESULTS: Cigarette smoking has been increasingly shown in epidemiologic and case-control studies to be an important risk factor for both the incidence and severity of RA, especially in seropositive men. Further, there is evidence of a downward trend in incidence of extra-articular manifestations of RA, especially RA vasculitis, observed with a decrease in worldwide tobacco use and overall improved mortality in RA. The association of cigarette smoking with lung and other cancers and its link to vascular disease (including Buerger's disease) and atherosclerosis appears secure. Mutations or alterations in p53, a suppressor gene that regulates cell growth, have been found in certain cancers, cigarette smokers, and in patients with RA. CONCLUSIONS: Cigarette smoking appears to have an undeniable link to the pathogenesis of vascular disease of many types, including the possibility of a strong causal connection to rheumatoid vasculitis. The observations worldwide of decreasing tobacco use along with secular trends of diminished RA vasculitis and extra-articular manifestations, and with improved survival, points to a better outcome for our patients. The example of p53 may be a first step in the discovery of additional links between environmental triggers and phenotypic expression of chronic illness.

The soluble CD40 ligand sCD154 in systemic lupus erythematosus.

We found that the plasma of patients with active systemic lupus erythematosus (SLE) could induce a human B-cell line (Ramos) to express high levels of immune accessory molecules that are commonly found on blood B cells of patients with active SLE. The ability of SLE plasma to induce such phenotypic changes could be abrogated by neutralizing antibodies specific for the CD40 ligand (CD154) but not by antibodies to TNF-alpha. Immunoprecipitation studies with anti-CD154 identified a 20-kDa protein in the plasma of SLE patients with active disease, but not in plasma of normal donors, indicating that such plasma contained soluble CD154 (sCD154). Using a quantitative ELISA method, we found that the plasma of patients with active disease had levels of sCD154 that were significantly higher than those found in plasma of normal donors. Levels of CD154 transcripts in SLE blood lymphocytes correlated with the relative concentrations of sCD154 found in SLE plasma. Furthermore, plasma levels of sCD154 correlated with the titers of anti-double-stranded DNA autoantibody and with clinical disease activity. These studies indicate that sCD154 of patients with SLE may act as a functional ligand for CD40 that is associated with SLE disease activity.