Caudal autotomy as anti-predatory behaviour in Palaeozoic reptiles.

Many lizards can drop a portion of their tail in response to an attack by a predator, a behaviour known as caudal autotomy. The capacity for intravertebral autotomy among modern reptiles suggests that it evolved in the lepidosaur branch of reptilian evolution, because no such vertebral features are known in turtles or crocodilians. Here we present the first detailed evidence of the oldest known case of caudal autotomy, found only among members of the Early Permian captorhinids, a group of ancient reptiles that diversified extensively and gained a near global distribution before the end-Permian  mass extinction event of the Palaeozoic. Histological and SEM evidence show that these early reptiles were the first amniotes that could autotomize their tails, likely as an anti-predatory behaviour. As in modern iguanid lizards, smaller captorhinids were able to drop their tails as juveniles, presumably as a mechanism to evade a predator, whereas larger individuals may have gradually lost this ability. Caudal autotomy in captorhinid reptiles highlights the antiquity of this anti-predator behaviour in a small member of a terrestrial community composed predominantly of larger amphibian and synapsid predators.

The silencing of cathepsin K used in gene therapy for periodontal disease reveals the role of cathepsin K in chronic infection and inflammation.

BACKGROUND AND OBJECTIVE: Periodontitis is a severe chronic inflammatory disease and one of the most prevalent non-communicable chronic diseases that affects the majority of the world's adult population. While great efforts have been devoted toward understanding the pathogenesis of periodontitis, there remains a pressing need for developing potent therapeutic strategies for targeting this dreadful disease. In this study, we utilized adeno-associated virus (AAV) expressing cathepsin K (Ctsk) small hairpin (sh)RNA (AAV-sh-Ctsk) to silence Ctsk in vivo and subsequently evaluated its impact in periodontitis as a potential therapeutic strategy for this disease. MATERIAL AND METHODS: We used a known mouse model of periodontitis, in which wild-type BALB/cJ mice were infected with Porphyromonas gingivalis W50 in the maxillary and mandibular periodontium to induce the disease. AAV-sh-Ctsk was then administrated locally into the periodontal tissues in vivo, followed by analyses to assess progression of the disease. RESULTS: AAV-mediated Ctsk silencing drastically protected mice (> 80%) from P. gingivalis-induced bone resorption by osteoclasts. In addition, AAV-sh-Ctsk administration drastically reduced inflammation by impacting the expression of many inflammatory cytokines as well as T-cell and dendritic cell numbers in periodontal lesions. CONCLUSION: AAV-mediated Ctsk silencing can simultaneously target both the inflammation and bone resorption associated with periodontitis through its inhibitory effect on immune cells and osteoclast function. Thereby, AAV-sh-Ctsk administration can efficiently protect against periodontal tissue damage and alveolar bone loss, establishing this AAV-mediated local silencing of Ctsk as an important therapeutic strategy for effectively treating periodontal disease.

Phagocytosis of wear debris by osteoblasts affects differentiation and local factor production in a manner dependent on particle composition.

Wear debris is considered to be one of the main factors responsible for aseptic loosening of orthopaedic endoprostheses. Whereas the response of cells in the monocytic lineage to foreign materials has been extensively studied, little is known about cells at the bone formation site. In the present study, we examined the hypothesis that the response of osteoblasts to wear debris depends on the chemical composition of the particles. We produced particles from commercially pure titanium (cpTi), Ti-6Al-4V (Ti-A), and cobalt-chrome (CoCr) and obtained ultrahigh molecular weight polyethylene (UHMWPE; GUR 4150) particles from a commercial source. The equivalent circle diameters of the particles were comparable: 1.0 +/- 0.96 microm for UHMWPE; 0.84 +/- 0.12 microm for cpTi; 1.35 +/- 0.09 microm for Ti-A, and 1.21 +/- 0.16 microm for CoCr. Confluent primary human osteoblasts and MG63 osteoblast-like cells were incubated in the presence of particles for 24 h. Harvested cultures were examined by transmission electron microscopy to determine if the cells had phagocytosed the particles. Particles were found intracellularly, primarily in the cytosol, in both the primary osteoblasts and MG63 cells. The chemical composition of the particles inside the cells was confirmed by energy-dispersive X-ray analysis. Morphologically, both cell types had extensive ruffled cell membranes, less-developed endoplasmic reticulum, swollen mitochondria, and vacuolic inclusions compared with untreated cells. CpTi, Ti-A, and CoCr particles were also added to cultures of MG63 cells to assess their effect on proliferation (cell number) and differentiation (alkaline phosphatase activity), and PGE2 production. All three types of particles had effects on the cells. The effect on cell number was dependent on the chemical composition of the particles; Ti-A and CoCr caused a dose-dependent increase, while cpTi particles had a biphasic effect with a maximal increase in cell number observed at the 1:10 dilution. Alkaline phosphatase specific activity was also affected and cpTi was more inhibitory than Ti-A or CoCr. PGE2 production was increased by all particles, but the magnitude of the effect was particle-dependent: CoCr > cpTi > Ti-A. This study demonstrates clearly that human osteoblast-like cells and MG63 cells can phagocytose small UHMWPE, CoCr, Ti-A, and cpTi particles. Phagocytosis of the particles is correlated with changes in morphology, and analysis of MG63 response shows that cell proliferation, differentiation, and prostanoid production are affected. This may have negative effects on bone formation adjacent to an orthopaedic implant and may initiate or contribute to the cellular events that cause aseptic loosening by inhibiting bone formation. The effects on alkaline phosphatase and PGE2 release are dependent on the chemical composition of the particles, suggesting that both the type and concentration of wear debris at an implant site may be important in determining clinical outcome.

The UTHSCSA Dental School in the new millennium.

The UTHSCSA Dental School, just short of 30 years in existence, has made great strides to be a leader in dental education. Although increased use of computers has the greatest potential for revolutionizing dental education, there are other components that must constantly be evaluated and improved. A major curriculum review is in progress. The process is a grass roots effort to allow input from faculty, students, alumni and outside consultants. The school's competencies are being reevaluated to assure they are contemporary and the methods to assess them are valid and reliable. The way we evaluate applicants is an ongoing evolution. Our appropriate role in the community (local, national, and international) continues to be a challenge. Success will be measured by how well we continuously evaluate our mission and goals, identify problems and find and implement solutions.

Comparison of natural with clomiphene citrate-stimulated cycles in in vitro fertilization: a prospective, randomized trial.

OBJECTIVE: To compare the outcome of natural with clomiphene citrate (CC)-stimulated cycles in IVF. DESIGN: Prospective, randomized study. SETTING: Tertiary referral center for assisted conception. SUBJECTS: Thirty patients randomized to receive either no treatment (n = 14) or CC, 100 mg, from days 2 to 6 (n = 16). INTERVENTIONS: Daily ultrasound (US) scan and measurements of serum LH and E2. Ovarian morphology was assessed on baseline US scan. Human chorionic gonadotrophin was administered when the mean diameter of the dominant follicle reached 17 mm. Transvaginal US-directed oocyte recovery was performed 35 hours later. MAIN OUTCOME MEASURES: The number of patients reaching oocyte recovery; numbers of oocytes collected, fertilized and embryos transferred; and clinical pregnancy and multiple pregnancy rates (PRs) were recorded. RESULTS: Ten cycles in the natural cycle group were abandoned before oocyte recovery compared with none in the CC group. There were significantly more follicles > 14 mm (2.4 +/- 0.3 [SE] compared with 0.9 +/- 0.2) and higher peak levels of E2 (375 +/- 67 pg/mL (1,378 +/- 247 pmol/L) compared with 204 +/- 17 pg/mL (748 +/- 61 pmol/L)) in those receiving CC compared with those receiving no drug. All 16 patients treated with CC had oocyte retrieval (mean, 1.8 +/- 0.3 oocytes) compared with only 4 in the natural cycle group (1 oocyte each). The oocyte recovery rate was 95%. Two patients conceived in the CC group (PR per ET, 18%) compared with none in the natural cycle group. Patients with polycystic ovaries developed more large follicles than those with normal ovaries. No patient developed ovarian hyperstimulation syndrome. CONCLUSIONS: Patients undergoing natural cycle IVF are more likely to have abandoned cycles, produce fewer follicles and oocytes, and are less likely to reach ET than patients treated with CC alone. Clomiphene citrate should be considered for use in the context of a conventionally organised IVF-ET program if a mild degree of ovarian stimulation is desired.

A controlled study comparing patients with and without polycystic ovaries undergoing in-vitro fertilization.

The outcome of in-vitro fertilization and embryo transfer (IVF-ET) was compared in 76 patients with polycystic ovaries (PCO) diagnosed on pre-treatment ultrasound scan, and 76 control patients who had normal ovaries and were matched for age, cause of infertility and stimulation regimen. Despite receiving significantly less human menopausal gonadotrophin (HMG), patients with PCO, as compared with controls, had significantly higher serum oestradiol levels on the day of human chorionic gonadotrophin administration (5940 +/- 255 versus 4370 +/- 240 pmol/l, P < 0.001), developed more follicles (14.9 +/- 0.7 versus 9.8 +/- 0.6, P < 0.001) and produced more oocytes (9.3 +/- 0.6 versus 6.8 +/- 0.5, P = 0.003). However, fertilization rates were reduced in the PCO patients (52.8 +/- 3.4% versus 66.1 +/- 3.4%, P = 0.007). There was no significant difference in cleavage rates. The pregnancy rate/embryo transfer was 25.4% in the PCO group and 23.0% in the group with normal ovaries. There were three high order multiple pregnancies in the PCO group compared with none in the group with normal ovaries. Of the PCO patients, 10.5% developed moderate/severe ovarian hyperstimulation syndrome (OHSS) compared with none of the controls (P = 0.006). Patients with and without PCO undergoing IVF have comparable pregnancy and livebirth rates. However, it is important to diagnose PCO before ovarian stimulation is initiated as these patients are more likely to develop moderate or severe OHSS following IVF-ET.

In-vitro fertilization and the ovarian hyperstimulation syndrome.

Eight patients who developed severe ovarian hyperstimulation syndrome (OHSS) were identified among 1302 patients undergoing in-vitro fertilization (IVF) over a 1 year period (prevalence of 0.6%); 63% had ultrasonically diagnosed polycystic ovaries (PCO) and 75% were undergoing their first attempt at IVF. Pretreatment with a superactive luteinizing hormone-releasing hormone (LHRH) analogue significantly increased the prevalence of severe OHSS (1.1% versus 0.2%, P less than 0.05) compared with ovarian stimulation with clomiphene citrate and human menopausal gonadotrophin (HMG). The mean serum oestradiol concentration on the day of human chorionic gonadotrophin (HCG) administration was 8200 +/- 2300 pmol/l. A mean of 19.6 +/- 6.8 follicles had been aspirated and 13.1 +/- 7.7 oocytes recovered at transvaginal ultrasound-directed oocyte recovery. All patients had an embryo transfer and luteal support in the form of HCG. The clinical pregnancy rate was 88%, multiple pregnancy rate 71% and implantation rate 63.5 +/- 41.3%. In a group of seven patients who were hospitalized for moderate OHSS during the same period, peak oestradiol levels were significantly lower than in those with severe OHSS (P less than 0.05). Of the group with moderate OHSS, 57% had PCO, the clinical pregnancy rate was 100% and multiple pregnancy rate 43%. Patients with ultrasound-diagnosed PCO have an increased risk of developing OHSS and the dose of HMG administered to them should be minimized. In patients at risk of developing OHSS, progesterone instead of HCG should be used for luteal support. Transfer of a maximum of two embryos or freezing all embryos for transfer in a subsequent cycle may reduce the likelihood of multiple pregnancy.