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.

Reliability of Chair-side Monolithic CAD-CAM Generated Lithium Disilicate Single Crowns with Knife- Edge Finish Line: Up to 5-Year Retrospective Analysis of Clinical Performance.

This clinical study evaluated the survival of monolithic lithium disilicate (MLD) single crowns. Between January-2010 and January-2015, 87 patients received 122 MLD (IPS e.max CAD) single crowns on natural teeth with knife-edge finish lines that were adhesively bonded (Maxcem Elite). MLD single crowns (N=122) were bonded on 60 molars (maxilla:35, mandible:25), 53 premolars (maxilla:27, mandible:26), 4 canines (maxilla:2, mandible:2), 3 laterals and 2 centrals (maxilla). One crown fracture, one retention loss and one endodontic complication were experienced (survival rate: 97.5%). MLD single crowns could be safely indicated on teeth with knife-edge preparations.

Hard and soft tissue changes in the rehabilitation of the anterior maxilla with triangular shape neck implants: a retrospective clinical study with a one-year follow up.

Aim of this retrospective study was to evaluate the one-year clinical and radiographic outcomes of implants with a triangular shaped neck inserted immediately after tooth extraction in esthetic zones. Patients in which immediate postextraction implants were placed and restored in the anterior maxilla, who underwent a Cone Beam Computed Tomograpy (CBCT) at baseline and after 12-16 months were included. The socket was preserved using deproteinized bovine bone to fill the buccal gap, and a resorbable collagen membrane. One-year implant survival and prosthesis success were evaluated. Hard and soft tissue stability was assessed by measuring various parameters on CBCT images. Clinical evaluation was also performed and Pink Esthetic Score (PES) assessed. Data from baseline and one-year follow-up were statistically compared using paired tests and a significance threshold of p=0.05. Twenty patients (13 males, 7 females, mean age 50.42±11.35 years) were included. Each contributed with one implant. No implant was lost. A significant improvement in PES was detected. Excellent hard and soft tissue preservation was observed after one year of function. Immediate placement of implants with a triangular shaped neck after tooth extraction, can be a suitable solution even for areas with a high aesthetic demand, such as the anterior maxilla.

A randomized, controlled clinical trial to evaluate the immunogenicity of a PreS/S hepatitis B vaccine Sci-B-Vac™, as compared to Engerix B®, among vaccine naïve and vaccine non-responder dialysis patients.

BACKGROUND: Dialysis patients have a suboptimal response to hepatitis B (HBV) vaccination. This study aimed to compare the immunogenicity of two vaccines: the third-generation Sci-B-Vac™ vs. the second-generation Engerix B®. The cohort included two groups of dialysis patients: naïve and previously vaccinated non-responders. Primary endpoints were antibody titers ≥10 IU/L at 3 and 7 month post-vaccination. Secondary objectives were seroprotection rates in vaccine-naïve patients and in previously vaccinated non-responders. METHODS: Eighty-six patients were assigned to vaccine (Sci-B-Vac™ or Engerix B®) using computer-generated randomization, stratified by age, gender, diabetes, and previous HBV vaccination. Sci-B-Vac™ was administered in three doses, 10 µg, at 0, 1, and 6 months in naïve patients; or 20 µg in previously vaccinated non-responders. Engerix B® included four doses, 40 µg at 0, 1, 2, and 6 months. RESULTS: Each group had 43 patients. Seroconversion was 69.8% with Engerix B® vs. 73.2% with Sci-B-Vac™. Antibody titers at 7 months were higher with Sci-B-Vac™ (266.4 ± 383.9, median 53.4) than with Engerix® (193.2 ± 328.9, median 19). However, these differences were not significant, perhaps due to a suboptimal sample size. CONCLUSIONS: This study suggests comparable immunogenicity for both vaccines. Thus, we cannot reject the null hypothesis that there is no difference in seroconversion by vaccine type. It is noteworthy that naïve patients were vaccinated with a standard dose of Sci-B-Vac™, while Engerix B® was administered at a double dose. Similarly, although mean antibody titer levels in the Sci-B-Vac™ group were higher than in the Engerix® group, this difference did not reach significance. Consequently, a future clinical trial should recruit a larger cohort of patients, using a standard double-dose protocol in both groups.

Morphological features of the maxillary incisors roots and relationship with neighbouring anatomical structures: possible implications in endodontic surgery.

The purpose of this study was to investigate the relationship between the root apex of the upper incisors and neighbouring anatomical structures as well as the morphology of the root-end foramen after apicoectomy. Fifty-seven patients requiring endodontic surgical treatment for a maxillary anterior root were enrolled. A preoperative diagnostic computed tomography (CT) scan was analysed to determine: the distance between the anterior wall of the nasopalatine duct and the central (CI-ND) incisor root 4mm from the apex; and the distance between the floor of the nasal cavity and the tip of either the central (CI-NF) or the lateral (LI-NF) incisor root. After apicoectomy, root-end foramen endoscopic pictures were taken in order to characterize their morphology. Fifty-nine central and 26 lateral incisors were evaluated. The average CI-ND was 4.71 ± 1.26 (SD) mm. The average CI-NF was 10.62 ± 2.25 mm. The average LI-NF was 13.05 ± 2.43 mm. The foramen shape after apicoectomy was ovoid to circular in about 90% of cases in both central and lateral incisors. A sound knowledge of the anatomical relationships at the surgical site is essential for the clinician to perform a safe endodontic surgical procedure.

Preservation of an injured vital tooth using ultrasonic device and mineral trioxide aggregate.

The purpose of this case report is to present a root fracture repair procedure for non devitalized injured tooth. One injured, non-endodontically treated maxillary anterior tooth in which an incomplete vertical root fracture involving only the buccal side was suspected, underwent an exploratory flap to visualize the pattern of bone loss and assess the type of root fracture. The pre-operative diagnosis was confirmed. A groove following fracture line was prepared using retro-tips driven by an ultrasonic device and sealed with Mineral Trioxide Aggregate (MTA), following filling of the bone defect with Calcium Sulphate. At 24 months follow up the case showed clinical and radiographic success. The present surgical approach showed preservation of function and vitality of tooth with a shallow incomplete vertical root fracture.

Effect of sevelamer hydrochloride exposure on carotid intima media thickness in hemodialysis patients.

BACKGROUND: Elevated phosphorus (P) and calcium (Ca)-P product (Ca × P) are associated with vascular calcification and cardiovascular disease (CVD) morbidity and CVD and all-cause mortality. OBJECTIVES: This study examined the effect of sevelamer hydrochloride exposure (regardless of calcium carbonate exposure) on carotid and femoral intima media thickness (IMT), reliable surrogate measures of prospective intimal thickening, in end-stage renal disease patients on maintenance hemodialysis. METHODS: The present cross-sectional study is nested in the Sevelamer hydrochloride and ultrasound-measured femoral and carotid intima media thickness progression in end-stage renal disease (SUMMER) clinical trial. Carotid and femoral arteries were visualized in B-mode ultrasonography. Log-transformed IMT was compared by sevelamer hydrochloride exposure and modeled using multiple linear regression. RESULTS: Forty-five subjects were exposed to sevelamer hydrochloride and 130 were not. Exposed subjects had significantly lower carotid IMT, an association which persisted in the multiple linear regression model even after controlling for potentially confounding variables including serum Ca, history of CVD and body weight. Exposed subjects had lower low-density lipoprotein cholesterol levels and significantly higher parathyroid hormone, but no differences in P, Ca and Ca × P. CONCLUSIONS: Sevelamer hydrochloride was associated with lower carotid IMT. This association may be mediated through reduction in Ca load, low-density lipoprotein cholesterol lowering or some other pleiotropic effect.

Endodontic treatment of a geminated maxillary second molar using an endoscope as magnification device.

AIM: To describe endodontic treatment for a rare case of gemination. SUMMARY: A case of complex endodontic treatment in a geminated tooth is presented. With the assistance of microinstruments and magnification devices, a geminated maxillary second molar was successfully treated. In such a case, ultrasonic tips and the use of an endoscope were essential to detect the peculiar anatomy of the tooth involved. KEY LEARNING POINTS: Knowledge of anomalies concerning fused teeth is essential. Using an endoscope as a magnification device is useful during the inspection of pulp chambers. Ultrasonic tips are safe and useful to detect canal orifices.

Magnification in modern endodontic practice.

The use of magnification devices in endodontics is becoming more and more common, with the aim of improving the quality of treatment. The common magnification systems used in modern endodontics are the surgical operation microscope, fiber-optic endoscope, and surgical loupes. The benefits of using magnification devices for conventional endodontic treatment include the increased visualization of the treatment field, enhanced possibilities in locating canals, aid in the removal of separated instruments, diagnosis of root and tooth fractures, perforation repair, and case documentation. In endodontic surgery, the use of magnification improves the ability to locate, clean, and fill the root canal system, thus achieving a predictable outcome. Further evidence-based research might better clarify the advantages and limitations of using magnification in endodontic practice.

The influence of previous non-surgical re-treatment on the outcome of endodontic surgery.

AIM: The aim of this study was to evaluate retrospectively if the outcome of periradicular surgery at four year follow-up can be affected by a previous orthograde re-treatment. METHODS: Eighty-one patients with 118 endodontically treated teeth who underwent surgical retreatment were divided in three groups. In group OA endodontic re-treatment was feasible and was attempted but, owing to the persistence of clinical symptoms and radiographic lesion, apical surgery was performed 4.8 ± 3.5 months later. In group OF endodontic re-treatment was feasible but was not performed, with subsequent apical surgery. In group ONF endodontic re-treatment was unfeasible, and apical surgery was performed. The treatment outcome was assessed four years postsurgery according to clinical and radiographic criteria. RESULTS: Seventy-six patients (112 teeth) could be evaluated at four years. In the ONF group five anterior maxillary teeth, belonging to three female patients, failed to heal. Three failures in three patients occurred in the OF group. No failure was recorded in the OA group. Three teeth in three patients were classified as uncertain healing in each group. The outcome of group OA resulted significantly better than the other treatment groups for both tooth-based and patient-based analysis. No significant effect was found as related to jaw, tooth type, presence of a post. A significant relation was found with gender (P=0.04). A negative correlation was found between outcome and age (Pearson's coefficient=-0.09), suggesting that the probability of failure increases with age. CONCLUSION: Orthograde re-treatment prior to apical surgery could be considered a valid alternative to tooth extraction and not an over-treatment.

Surgical decision making in coronally located vertical root fracture.

AIM: The purpose of this study was to present an intrasurgical decision making in teeth showing clinical signs and symptoms of incomplete vertical root fracture. METHODS: Sixteen patients with one tooth in which an incomplete vertical root fracture was diagnosed, involving only the buccal side, underwent a flap elevation procedure to visualize the pattern of bone loss and assess the type of root fracture. If the intraoperative diagnosis confirmed the presurgical one, a new root fracture repair technique was used. If the intraoperative diagnosis consisted of a complete or multiple fracture, the tooth was extracted and a postextraction implant insertion procedure was performed, in combination with the use of plasma rich in growth factors in order to enhance implant osseointegration. RESULTS: A total of nine vertical root fracture repair procedures were performed. The mean patient follow-up was 22.5 months. All patients reported full satisfaction for mastication function and phonetics. One patient was not satisfied for the esthetic result. A total of seven implants were immediately inserted in fresh postextraction sockets, and loaded four months later. The mean patient follow-up was 25.2 months. Overall implant success and survival was 100% after one year of functional loading. All patients reported full satisfaction for mastication function, phonetics and esthetics. CONCLUSIONS: Intraoperative diagnosis allowed to choose an appropriate surgical approach that led to excellent results in terms of clinical outcomes and patient satisfaction.

Effect of sodium hypochlorite with the addition of a proteolytic enzyme on postoperative discomfort: a multicenter randomized clinical trial.

AIM: The purpose of this study was to compare the patient's postoperative discomfort when root canal irrigation was performed either with standard sodium hypochlorite or with sodium hypochlorite with the adjunct of a proteolytic enzyme. METHODS: Two hundred patients were endodontically treated in two clinics. The type of irrigant to be used during root canal instrumentation was randomly assigned. Final irrigation was done using EDTA 17%. The canals were filled by warm vertical condensation with guttha-percha and the coronal seal was made using IRM. Patients were given a questionnaire to assess pain and swelling and the number of analgesics and other drugs taken during the first week after treatment. RESULTS: A total of 166 questionnaires could have been evaluated. No significant difference was found between groups for pain, swelling and analgesics taken. Moderate pain and swelling was reported only in the first two days after treatment. No antibiotics use was reported. No guttha-percha excess beyond root apex was found by radiographic assessment. CONCLUSIONS: The irrigating solution containing a proteolytic enzyme does not produce greater postoperative discomfort as compared to the conventional sodium hypochlorite in patients undergoing endodontic therapy.

Endoscopic management of a lateral root lesion. A case report.

The aim of this study was to obtain periradicular tissue healing of a lateral root lesion using a microsurgical technique. The case report concerns a 52-year-old female patient, in general good health (ASA1), presented with the left maxillary canine (2.3) exhibiting acute, specific symptoms. A radiographic examination revealed the presence of a circumscribed radiolucent lesion associated with the mesial mid-root area of the 2.3 and the distal mid-root area of 2.2, both endodontically treated. Using an endoscope as a magnification device a surgical inspection of the middle-third of the root of 2.2 and 2.3 was made. A pathway between the periodontium and root-canal system was detected with an endodontic file on the middle-third of 2.3 root wall. A root-lateral cavity was prepared using retro-tips. An EBA cement was used as the root-end filling material. Following clinical and radiographic assessment at 36 months post-surgery, the case was classified as successful. This case report showed the utility of using an endoscope and micro-surgical instruments for diagnosis and surgical treatment of micro-anatomical root structures.

Two-scale, three-phase theory for swelling drug delivery systems. Part I: constitutive theory.

Polymeric carriers used in drug delivery applications, such as hydroxypropyl methylcellulose, that swell significantly upon coming in contact with water (or biological fluid) have been historically difficult to model due to the complex interplay of forces. This article seeks to introduce a thermodynamically consistent framework in which to address such problems. Here, a constitutive theory is developed that is applicable to viscoelastic polymers carrying an initially elastic drug that subsequently dissolves when exposed to a viscous fluid. The theoretical model consists of three phases, the polymer, drug, and fluid. A novel form of Darcy's law is reported that clearly distinguishes between distortional and dilatational forces and accounts for the affect of polymer relaxation on fluid transport. A standard form of Fick's law is also derived.

Arginine uptake is attenuated through modulation of cationic amino-acid transporter-1, in uremic rats.

Endothelial cell dysfunction (ECD) is a common feature of chronic renal failure (CRF). Defective nitric oxide (NO) generation due to decreased endothelial NO synthase (eNOS) activity is a crucial parameter characterizing ECD. L-arginine is the sole precursor for NO biosynthesis. Among several transporters that mediate L-arginine uptake, cationic amino-acid transporter-1 (CAT-1) acts as the specific arginine transporter for eNOS. Our hypothesis implies that CAT-1 is a major determinant of eNOS activity in CRF. We studied glomerular and aortic arginine uptake, CAT-1, and CAT-2 messenger ribonucleic acid (mRNA) expression, and CAT-1 protein in: (a) rats 6 weeks following 5/6 nephrectomy (CRF), (b) sham-operated animals, and (c) rats with CRF treated orally with either atorvastatin or arginine in drinking water (modalities which have been shown to enhance eNOS activity and improve endothelial function). Both glomerular and aortic arginine transport were significantly decreased in CRF. Treatment with either arginine or atorvastatin abolished the decrease in arginine uptake in CRF rats. Using reverse transcriptase-polymerase chain reaction and Northern blotting, we found a significant increase in glomerular and aortic CAT-1 mRNA expression in CRF. Western blotting revealed that CAT-1 protein was decreased in CRF, but remained intact following arginine and atorvastatin administration. Renal and systemic arginine uptake is attenuated in CRF, through modulation of CAT-1 protein. These findings provide a possible novel mechanism to eNOS inactivation and endothelial dysfunction in uremia.

Peripheral vascular disease and serum phosphorus in hemodialysis: a nested case-control study.

BACKGROUND: Serum phosphorus (P) and the product of serum calcium x serum P (Ca x P), are frequently elevated in end-stage renal disease patients on maintenance hemodialysis (HD). Elevated P and Ca x P have been associated with vascular calcification in dialysis patients. OBJECTIVE: [corrected] To examine the role of P and Ca x P as risk factors for incident peripheral vascular disease (PVD) in HD patients with pre-existing CVD. METHODS: This nested case-control study is drawn from the 11 incident PVD events reported in the cohort of the Secondary prevention with antioxidants of cardiovascular disease in end-stage renal disease (SPACE): a randomized placebo-controlled trial. PVD was defined clinically and confirmed ultrasonographically. Each individual with a PVD event was matched for SPACE treatment group (vitamin E or placebo), age (in 4-year categories) and gender with two individuals who had no CVD end point during the follow-up period. RESULTS: Serum P and Ca x P levels were significantly higher in PVD patients than in controls. In univariate logistic regression analysis, only serum P predicted PVD in this population (OR 2.02, 95% CI 1.07 - 3.81, p = 0.03). In multivariate analysis, adjustment was made for variables dissimilar by PVD status including underlying renal disease, diabetes, smoking, history of angina pectoris, prescription for vitamin D3, erythropoietin, calcium channel blockers and aspirin. In this model, serum P remained the only significant predictor of incident PVD (OR 2.4, 95% CI 1.01 - 5.74, p = 0.04). CONCLUSIONS: Findings of the present study are consistent with a role for serum P and Ca x P in the pathogenesis of PVD in HD patients.

Orthostatic hypotension in the elderly: are the diagnostic criteria adequate?

Orthostatic hypotension (OH) is a common finding in the elderly. OH is defined as a fall of at least 20 mmHg in systolic blood pressure (BP) and/or 10 mmHg in diastolic BP upon assuming an upright posture. Some patients exhibit a fall in BP of less than the defined OH upon standing. The aim of this study was to estimate the prevalence of BP changes not defined as OH among elderly in-patients and to assess the relationship between these changes in the morning and the occurrence of OH during the day. Postural BP measurements were performed in 502 in-patients; in the morning, early afternoon, and in the evening. We defined intermediate postural drop (ID) in BP as a decrease of 10-19 mmHg in systolic BP and/or of 5-9 mmHg in diastolic BP. We observed that OH and ID occurred in 39.2 and 18.5% of the measurements in the morning, respectively. The prevalence of OH and ID was lower in the evening than in the morning (P<0.05) and afternoon (P<0.005). Postural BP changes in the morning correlated with those occurring later in the day. Patients who had ID in the morning had a 57% probability of having OH later during the day. In conclusions, ID is prevalent in elderly in-patients. ID in the morning predicts OH later in the day. Thus, postural BP drops below the OH range may be an important finding in the geriatric population.

Delayed branching of endothelial capillary-like cords in glycated collagen I is mediated by early induction of PAI-1.

Development of micro- and macrovascular disease in diabetes mellitus (DM) warrants a thorough investigation into the repertoire of endothelial cell (EC) responses to diabetic environmental cues. Using human umbilical vein EC (HUVEC) cultured in three-dimensional (3-D) native collagen I (NC) or glycated collagen I (GC), we observed capillary cord formation that showed a significant reduction in branching when cells were cultured in GC. To gain insight into the molecular determinants of this phenomenon, HUVEC subjected to GC vs. NC were studied using a PCR-selected subtraction approach. Nine different genes were identified as up- or downregulated in response to GC; among those, plasminogen activator inhibitor-1 (PAI-1) mRNA was found to be upregulated by GC. Western blot analysis of HUVEC cultured on GC showed an increase in PAI-1 expression. The addition of a neutralizing anti-PAI-1 antibody to HUVEC cultured in GC restored the branching pattern of formed capillary cords. In contrast, supplementation of culture medium with the constitutively active PAI-1 reproduced defective branching patterns in HUVEC cultured in NC. Ex vivo capillary sprouting in GC was unaffected in PAI-1 knockout mice but was inhibited in wild-type mice. This difference persisted in diabetic mice. In conclusion, the PCR-selected subtraction technique identified PAI-1 as one of the genes characterizing an early response of HUVEC to the diabetic-like interstitial environment modeled by GC and responsible for the defective branching of endothelial cells. We propose that an upregulation of PAI-1 is causatively linked to the defective formation of capillary networks during wound healing and eventual vascular dropout characteristic of diabetic nephropathy.

Hepatitis C infection in dialysis patients in Israel.

BACKGROUND: Hepatitis C virus is the major cause of acute and chronic hepatitis in patients with end-stage renal disease receiving replacement therapy. OBJECTIVES: To define the prevalence of HCV RNA in a population of patients on dialysis in Israel, to determine the relative risk of acquiring HCV infection while treated by hemodialysis or chronic ambulatory peritoneal dialysis, and to define the HCV genotypes in this population. METHODS: During 1995 we studied 162 dialysis patients. Information was obtained regarding the mode of dialysis, years of treatment, number of blood transfusions, and results of serological testing for HCV, hepatitis B virus, and human immunodeficiency virus. Anti-HCV antibodies were tested by a third-generation microparticle enzyme immunoassay. HCV RNA was determined by polymerase chain reaction. HCV genotyping was performed by a hybridization assay. RESULTS: HCV RNA was detected in 18% of the HD group and 7% of the CAPD group. The number of HCV RNA-positive patients was significantly higher in the HD than the CAPD group (P < 0.05). HCV RNA-positive HD patients were treated longer than the HCV RNA-negative patients (P < 0.02). CONCLUSIONS: Third-generation immunoassay proved to be highly sensitive (94%) and specific (91%) in identifying HCV RNA positivity. Several HCV subtypes were detected, 1b being the most frequent. Identification and isolation of infected HCV patients may minimize its spread in dialysis units and prevent cross-infection.

Mesna: a novel renoprotective antioxidant in ischaemic acute renal failure.

BACKGROUND: Reactive oxygen species (ROS) play a key role in renal ischaemia-reperfusion injury. After establishing the in vitro anti-oxidative potential of mesna, a sulfhydryl-containing compound, its effect on kidney function and morphology in a rat model of ischaemic acute renal failure (ARF) was examined. METHODS: Mesna (180 mg/kg) was administered at different time points relative to ischaemia and/or reperfusion onset. Kidney function was assessed by glomerular filtration rate (GFR) and fractional sodium excretion (FE(Na)) before a 45-min period of unilateral renal artery clamping and following 90 min of reperfusion. Mesna was administered by bolus, 30 min before the induction of ischaemia, 5 min before ischaemia, 5 min before reperfusion, and 5 min after the onset of reperfusion. RESULTS: Mesna improved function of the ischaemic kidney at each administration. When mesna was administered 5 min before the onset of reperfusion, GFR reached 90-100% of its pre ischaemic value and FE(Na) was improved by 75%. The beneficial effect of mesna was also demonstrated by light and electron microscopy. Kidneys treated with mesna 5 min before reperfusion resembled ischaemic non-reperfused kidneys and showed subtle morphological and ultrastructural changes compared with ischaemic-reperfused kidneys. Mesna had no haemodynamic effect on renal blood flow and did not induce any osmotic diuresis. CONCLUSIONS: We suggest that mesna acts as an antioxidant. Its antioxidant potential together with optimal protection achieved when administered 5 min before reperfusion, supports the conclusion that mesna scavenges ROS generated at the onset of reperfusion, thus diminishing reperfusion injury and organ damage.