Autologous stem cell transplantation for early type 1 diabetes mellitus

Type 1 diabetes mellitus (T1DM) is the result of the autoimmune response against pancreatic insulin producing cells. This autoimmune response begins months or even years before the first presentation of signs and symptoms of hyperglycemia and at the time of clinical diagnosis near 30% of -cell mass still remains. In daily clinical practice, the main therapeutic option for T1DM is multiple subcutaneous insulin injections that are shown to promote tight glucose control and reduce much of diabetic chronic complications, especially microvascular complications. Another important aspect related to long-term complications of diabetes is that patients with initially larger -cell mass suffer less microvascular complications and less hypoglycemic events than those patients with small -cell mass. In face of this, -cell preservation is another important target in the management of type 1 diabetes and its related complications. For many years, various immunomodulatory regimens were tested aiming at blocking autoimmunity against -cell mass and at promoting -cell preservation, mainly in secondary prevention trials. In this review, we summarize some of the most important studies involving -cell preservation by immunomodulation and discuss our preliminary data on autologous nonmyeloablative hematopoietic stem cell transplantation in newly-diagnosed T1DM.

TAC3/TACR3 Mutations Reveal Preferential Activation of Gonadotropin-Releasing Hormone Release by Neurokinin B in Neonatal Life Followed by Reversal in Adulthood

Context: Mutations in TAC3 and TACR3 (encoding neurokinin B and its receptor) have been identified in Turkish patients with idiopathic hypogonadotropic hypogonadism (IHH), but broader populations have not yet been tested and genotype-phenotype correlations have not been established. Objective: A broad cohort of normosmic IHH probands was screened for mutations in TAC3/TACR3 to evaluate the prevalence of such mutations and define the genotype/phenotype relationships. Design and Setting: The study consisted of sequencing of TAC3/TACR3, in vitro functional assays, and neuroendocrine phenotyping conducted in tertiary care centers worldwide. Patients or Other Participants: 345 probands, 18 family members, and 292 controls were studied. Intervention: Reproductive phenotypes throughout reproductive life and before and after therapy were examined. Main Outcome Measure: Rare sequence variants in TAC3/TACR3 were detected. Results: In TACR3, 19 probands harbored 13 distinct coding sequence rare nucleotide variants [three nonsense mutations, six nonsynonymous, four synonymous (one predicted to affect splicing)]. In TAC3, one homozygous single base pair deletion was identified, resulting in complete loss of the neurokinin B decapeptide. Phenotypic information was available on 16 males and seven females with coding sequence variants in TACR3/TAC3. Of the 16 males, 15 had microphallus; none of the females had spontaneous thelarche. Seven of the 16 males and five of the seven females were assessed after discontinuation of therapy; six of the seven males and four of the five females demonstrated evidence for reversibility of their hypogonadotropism. Conclusions: Mutations in the neurokinin B pathway are relatively common as causes of hypogonadism. Although the neurokinin B pathway appears essential during early sexual development, its importance in sustaining the integrity of the hypothalamic-pituitary-gonadal axis appears attenuated over time. (J Clin Endocrinol Metab 95: 2857-2867, 2010)

Role of dexamethasone on vasopressin release during endotoxemic shock

The present study was designed to assess the hypothesis that dexamethasone (DEX) through the control of nitric oxide (NO) synthesis could regulate the release of vasopressin (AVP), which plays an important role in the regulation of arterial pressure and plasma osmolality. Endotoxemic shock was induced by intravenous (i.v.) injection of 1.5 mg/kg lipopolisaccharide (LPS) in male Wistar rats weighing 250-300 g. After LPS administration, a group of animals were treated with DEX (1.0 mg/kg of body weight), whereas saline-injected rats served as controls. The LPS administration induced a significant decrease in mean arterial pressure (MAP) with a concomitant increase in heart rate (HR) (Delta VMAP: -16.1 +/- 4.2 mm Hg; Delta VHR: 47.3 +/- 8.1 bpm). An increase in plasma AVP concentration occurred and was present for 2 h after LPS administration (11.1 +/- 0.9 pg/mL) returning close to basal levels thereafter and remaining unchanged until the end of the experiment. When LPS was combined with i.v. administration of a low dose of DEX, we observed an attenuation in the drop of MAP (Delta VMAP: -2.2 +/- 1.9 mm Hg) and a decrease in NO plasma concentration [NO] after LPS administration (1098.1 +/- 68.1 mu M) compared to [NO] after DEX administration (523.4 +/- 75.2 mu M). However, this attenuation in the drop of MAP was accompanied by a decrease in AVP plasma concentration (3.7 +/- 0.4 pg/mL). These data suggest that AVP does not participate in the recovery of MAP when DEX is administered in this endotoxemic shock model. (C) 2008 Elsevier B.V. All rights reserved.

The Impact of Preexisting Myocardial Remodeling on Ventricular Function Early after Tetralogy of Fallot Repair

Background: Twenty-three patients (median age 23 months) who underwent Fallot`s tetralogy repair were investigated prospectively to detect a possible association between histopathologic myocardial remodeling and echocardiographic findings of systolic or diastolic ventricular dysfunction. Methods: Intraoperatively resected infundibular bands and subendocardial biopsy samples from the right ventricle (RV) and left ventricle were obtained for histopathologic evaluation. Tissue Doppler echocardiographic interrogation of the ventricles was performed before surgery and in the postoperative period. Results: Histopathologic data revealed hypertrophy of the RV cardiomyocytes and increased interstitial collagen in both ventricles. Mean values of RV isovolumic acceleration decreased significantly at the third evaluation compared with the preoperative values (P = .006). RV myocardial fibrosis greater than 8.3% was associated with a probability of altered E` of at least 0.7 (odds ratio = 2.31). Conclusion: Preoperative histologic myocardial remodeling influenced the postoperative RV function in this group of patients with late repair. Further studies are necessary to evaluate the myocardium in younger patients and to define its influence in the long-term follow-up. (J Am Soc Echocardiogr 2010;23:912-8.)

Effects of adhesive temperature on the early and 6-month dentin bonding

Objectives: The aim of this study was to test the effect of adhesive temperature on the bond strength to dentin (mu TBS) and silver nitrate uptake (SNU) of an ethanol/water (Adper Single Bond 2 [SB]) and an acetone-based (Prime&Bond 2.1 [PB]) etch-and-rinse adhesive system. Methods: The bottles of each adhesive were kept in various temperatures (5 degrees C, 20 degrees C, 37 degrees C and 50 degrees C) for 1 h previously to its application in the occlusal demineralized dentin of 40 molars. Bonded sticks (0.8 mm(2)) were tested in tension (0.5 mm/min) immediately (IM) or after 6 months (6 M) of water storage. Two bonded sticks from each hemi-tooth were immersed in silver nitrate and analyzed by SEM. Data were analyzed by two-way repeated measures ANOVA and Tukey`s test (alpha = 0.05). Results: No significant difference in mu TBS was detected for both adhesives at 5 degrees C and 20 degrees C. The highest bond strength for PB was observed in the 37 degrees C group while for SB it was in the 50 degrees C. Significant reductions of bond strengths were observed for PB at 37 degrees C and SB at 50 degrees C after 6 M of water storage. Silver nitrate deposition was seen in all hybrid layers, irrespective of the group. Lower silver nitrate deposition (water trees) in the adhesive layer was seen for PB and SB at higher temperatures. Conclusions: The heating or refrigeration of the adhesives did not improve their resin-dentin bond resistance to water degradation over time. (C) 2009 Elsevier Ltd. All rights reserved.

Early and 24-hour bond strength and degree of conversion of etch-and-rinse and self-etch adhesives

Purpose: To evaluate early and 24-hour microtensile bond strength (mu TBS) and the degree of conversion (DC) of one representative adhesive system from each of the four current bonding approaches. Methods: 40 human molars were sectioned occluso-gingivally into two halves. Resin composite was bonded incrementally to flat, mid-coronal dentin, using the adhesives Adper Scotchbond MP (MP); Adper Scotchbond 2 (SB); Clearfil SE Bond (SE); and Adper Prompt L-Pop (LP) according to the respective manufacturer`s instructions (n= 10). One half was immediately sectioned into sticks and subjected to mu TBS test. As the sectioning process took approximately 1 hour, the results were designated as 1-hour bond strengths. The other half was stored in distilled water at 37 degrees C for 24 hours before being sectioned and tested. The DC of these systems was measured using Fourier Transform-Raman spectroscopy in three periods: immediately, 1 and 24 hours after polymerization. Data were analyzed with ANOVA and Tukey`s tests. Results: There were no significant differences between the 1-hour and 24-hour bond strengths (P> 0.05), or among the DC measured immediately, 1 hour and 24 hours after polymerization (P> 0.05). However, significant differences were observed among adhesives (P< 0.05). mu TBS values obtained, in MPa (1 hour/24 hour), were: SB (48.6 + 1.3/48.4 + 3.5) = SE (51.9 + 4.7/53.3 +/- 2.9) > MP (35.3 +/- 10.9/38.6 + 6.7) > LP (25.5 + 1.1/26.0 + 1.5). The DC, in percentage (immediately/1 hour/24 hour), were: SE (81/82/87) > MP (79/77/81) > SB (60/63/65) > LP (39/37/42).

pH, Calcium Ion Release, and Setting Time of an Experimental Mineral Trioxide Aggregate-based Root Canal Sealer

Introduction: An experimental mineral trioxide aggregate sealer (MTAS) has been developed for use as a root canal sealer. The aim of this study was to evaluate the setting time, pH, and calcium ion release of MTAS compared with white Portland cement (CPB-40; Votorantin Cimentos, Camargo Correa SA, Pedro Leopoldo, MG, Brazil), white MTA Angelus (MTA; Angelus, Londrina, PR, Brazil), and AH Plus (Dentsply DeTrey, Konstanz, Germany). Methods: For the evaluation of setting time, each material was analyzed using Gilmore-type needles. Polyethylene tubes with the materials were immersed in distilled water for the measurement of pH (digital pH meter) and calcium release (atomic absorption spectrophotometry). The evaluations were performed at 3, 6, 12, 24, and 48 hours and 7, 14, and 28 days. Data were analyzed by analysis of variance and the Tukey test at 5% significance level. Results: MTAS showed higher calcium release at all experimental periods, a greater increase in pH up to 48 hours and the longest setting time. Conclusions: MTAS presented favorable properties for its indication as a root canal sealer. (J Endod 2011;37:844-846)

Heat Release, Time Required, and Cleaning Ability of Mtwo R and ProTaper Universal Retreatment Systems in the Removal of Filling Material

Introduction: This ex vivo study evaluated the heat release, time required, and cleaning efficacy of MTwo (VDW, Munich, Germany) and ProTaper Universal Retreatment systems (Dentsply/Maillefer, Ballaigues, Switzerland) and hand instrumentation in the removal of filling material. Methods: Sixty single-rooted human teeth with a single straight canal were obturated with gutta-percha and zinc oxide and eugenol-based cement and randomly allocated to 3 groups (n = 20). After 30-day storage at 37 degrees C and 100% humidity, the root fillings were removed using ProTaper UR, MTwo R, or hand files. Heat release, time required, and cleaning efficacy data were analyzed statistically (analysis of variance and the Tukey test, alpha = 0.05). Results: None of the techniques removed the root fillings completely. Filling material removal with ProTaper UR was faster but caused more heat release. Mtwo R produced less heat release than the other techniques but was the least efficient in removing gutta-percha/sealer. Conclusions: ProTaper UR and MTwo R caused the greatest and lowest temperature increase on root surface, respectively; regardless of the type of instrument, more heat was released in the cervical third. Pro Taper UR needed less time to remove fillings than MTwo R. All techniques left filling debris in the root canals. (I Endod 2010;36:1870-1873)

Effect of Smoking on Early Bone Healing Around Oxidized Surfaces: A Prospective, Controlled Study in Human Jaws

Background: This prospective and controlled histologic study evaluates the impact of smoking on bone-to-implant contact, the bone density in the threaded area, and the bone density outside the threaded area around microimplants with anodized surface retrieved from human jaws. Methods: A total of 24 subjects (mean age 51.32 +/- 7.5 years) were divided in two groups: smokers (n = 13 subjects) and non-smokers (n = 11 subjects). Each subject received one microimplant with oxidized surface during conventional mandible or maxilla implant surgery. After 8 weeks, the microimplants and the surrounding tissue were removed and prepared for histomorphometric analysis. Results: Three microimplants placed in smokers showed no osseointegration. The newly formed bone showed early stages of maturation, mainly in the non-smokers. Marginal bone loss, gap, and fibrous tissue were present around implants retrieved from smokers. Histometric evaluation indicated that the mean bone-to-implant contact ranged between 25.97% +/- 9.02% and 40.01% +/- 12.98% for smokers and non-smokers, respectively (P <0.001). Smokers presented 28.17% +/- 10.32% of bone density in the threaded area, whereas non-smokers showed 46.34% +/- 19.12%. The mean of bone density outside the threaded area ranged between 18.76% and 25.11% for smokers and non-smokers, respectively (P>0.05). Conclusion: The present data obtained in human subjects confirm that smoking has a detrimental effect on early bone tissue response around oxidized implant surfaces. J Periodontol 2010;81:575-583.

Effect of laser phototherapy on the release of fibroblast growth factors by human gingival fibroblasts

The effects of laser phototherapy on the release of growth factors by human gingival fibroblasts were studied in vitro. Cells from a primary culture were irradiated twice (6 h interval), with continuous diode laser [gallium-aluminum-arsenium (GaAlAs), 780 nm, or indium-gallium-aluminum-phosphide (InGaAlP),_660 nm] in punctual and contact mode, 40 mW, spot size 0.042 cm(2), 3 J/cm(2) and 5 J/cm(2) (3 s and 5 s, respectively). Positive [10% fetal bovine serum (FBS)] and negative (1%FBS) controls were not irradiated. Production of keratinocyte growth factor (KGF) and basic fibroblast growth factor (bFGF) was quantified by enzyme-linked immunosorbent assay (ELISA). The data were statistically compared by analysis of variance (ANOVA) followed by Tukey`s test (P a parts per thousand currency signaEuro parts per thousand 0.05). The characterization of the cell line indicated a mesenchymal nature. KGF release was similar in all groups, while that of bFGF was significantly greater (1.49-times) in groups treated with infra-red laser. It was concluded that increased production of bFGF could be one of the mechanisms by which infra-red laser stimulates wound healing.

Evaluation of pH and Calcium Ion Release of Calcium Hydroxide Pastes Containing Different Substances

Introduction: The objective of this study was to evaluate the pH and calcium ion release of calcium hydroxide pastes associated with different substances. Methods: Forty acrylic teeth with simulated root canals were divided into 4 groups according to the substance associated to the calcium hydroxide paste: chlorhexidine (CHX) in 2 formulations (1% solution and 2% gel), Casearia sylvestris Sw extract, and propylene glycol (control). The teeth with pastes and sealed coronal accesses were immersed in 10 mL deionized water. After 10 minutes, 24 hours, 48 hours, and 7, 15, and 30 days, the teeth were removed to another container, and the liquid was analyzed. Calcium ion release was measured by atomic absorption spectrophotometry, and pH readings were made with a pH meter. Data were analyzed statistically by analysis of variance and Tukey test (alpha = 0.05). Results: Calcium analysis revealed significant differences (P < .05) for 1% CHX solution and 2% CHX gel at 10 minutes. After 24 hours, 2% CHX gel x Control and 2% CHX gel x 1% CHX solution differed significantly (P < .05). After 48 hours, there were significant differences (P < .05) for 2% CHX gel x Control and Extract x Control. No differences (P > .05) were observed among groups in the other periods. Regarding the pH, there were significant differences (P < .05) for 2% CHX gel x Control and 2% CHX gel x 1% CHX solution after 48 hours and for 2% CHX gel x Control after 15 days. In the other periods, no differences (P > .05) were observed among groups. Conclusions: All pastes behaved similarly in terms of pH and calcium ion release in the studied periods. (J Endod 2009;35:1274-1277)

Comparison of pulmonary vascular function and structure in early and established hypoxic pulmonary hypertension in rats

In pulmonary hypertension, changes in pulmonary vascular structure and function contribute to the elevation in pulmonary artery pressure. The time-courses for changes in function, unlike structure, are not well characterised. Medial hypertrophy and neomuscularisation and reactivity to vasoactive agents were examined in parallel in main and intralobar pulmonary arteries and salt-perfused lungs from rats exposed to hypoxia (10% O-2) for 1 and 4 weeks (early and established pulmonary hypertension, respectively). After 1 week of hypoxia, in isolated main and intralobar arteries, contractions to 5-hydroxytryptamine and U46619 (thromboxane-mimetic) were increased whereas contractions to angiotensins I and II and relaxations to acetylcholine were reduced. These alterations varied quantitatively between main and intralobar arteries and, in many instances, regressed between 1 and 4 weeks. The alterations in reactivity did not necessarily link chronologically with alterations in structure. In perfused lungs, constrictor responses to acute alveolar hypoxia were unchanged after 1 week but were increased after 4 weeks, in conjunction with the neomuscularisation of distal alveolar arteries. The data suggest that in hypoxic pulmonary hypertension, the contribution of altered pulmonary vascular reactivity to the increase in pulmonary artery pressure may be particularly important in the early stages of the disease.

Trends in cigarette smoking in 36 populations from the early 1980s to the mid-1990s: Findings from the WHO MONICA Project

Objectives. This report analyzes cigarette smoking over 10 years in populations in the World Health Organization (WHO) MONICA Project (to monitor trends and determinants of cardiovascular disease). Methods. Over 300 000 randomly selected subjects aged 25 to 64 years participated in surveys conducted in geographically defined populations. Results. For men, smoking prevalence decreased by more than 5% in 16 of the 36 study populations, remained static in most others, but increased in Beijing. Where prevalence decreased, this was largely due to higher proportions of never smokers in the younger age groups rather than to smokers quitting. Among women, smoking prevalence increased by more than 5% in 6 populations and decreased by more than 5% in 9 populations. For women, smoking tended to increase in populations with low prevalence and decrease in populations with higher prevalence; for men, the reverse pattern was observed. Conclusions. These data illustrate the evolution of the smoking epidemic in populations and provide the basis for targeted public health interventions to support the WHO priority for tobacco control.

Timing and magnitude of peak height velocity and peak tissue velocities for early, average, and late maturing boys and girls

Height, weight, and tissue accrual were determined in 60 male and 53 female adolescents measured annually over six years using standard anthropometry and dual-energy X-ray absorptiometry (DXA). Annual velocities were derived, and the ages and magnitudes of peak height and peak tissue velocities were determined using a cubic spline fit to individual data. Individuals were rank ordered on the basis of sex and age at peak height velocity (PHV) and then divided into quartiles: early (lowest quartile), average (middle two quartiles), and late (highest quartile) maturers. Sex- and maturity-related comparisons in ages and magnitudes of peak height and peak tissue velocities were made. Males reached peak velocities significantly later than females for all tissues and had significantly greater magnitudes at peak. The age at PHV was negatively correlated with the magnitude of PHV in both sexes. At a similar maturity point (age at PHV) there were no differences in weight or fat mass among maturity groups in both sexes. Late maturing males, however, accrued more bone mineral and lean mass and were taller at the age of PHV compared to early maturers. Thus, maturational status (early, average, or late maturity) as indicated by age at PHV is inversely related to the magnitude and late maturers for weight and fat mass in boys and girls. Am. J. Hum. Biol. 13:1-8, 2001. (C) 2001 Wiley-Liss, Inc.

Child-Pugh class, nutritional indicators and early liver transplant outcomes

Background/Aims: Patients with chronic liver disease undergoing liver transplantation have reduced body fat and muscle mass. The extent to which nutritional indicators and Child-Pugh class are predictive of postoperative outcome in adults is unclear. The aims of this study were to determine in adult patients undergoing transplant 1) the influence of preoperative Child-Pugh class and nutritional indicators on early transplant outcomes and one-year survival, 2) the relationship between nutritional indicators and Child-Pugh class and disease type. This study included 80 patients (1990-1994). Methodology: The nutritional indicators utilized were grip strength, triceps skinfold thickness and uncorrected mid-arm muscle area. Measured outcomes were ventilator time, intensive care stay, postoperative hospital stay and one-year survival. Results: Early morbidity was determined in survivors. Child-Pugh class C patients required longer ventilation and spent more time in the intensive care unit than Child-Pugh classes A and B. No significant relationships were found length of hospital stay. Relationships between the nutritional indicators (when controlled for Child-Pugh class) and early morbidity could not be determined due;to insufficient data. No relationship was established between one-year survival and Child-Pugh class or the nutritional indicators. Grip strength and mid-arm muscle area were lower in the patients in Child-Pugh:classes B and C. Parenchymal liver disease was associated with lower grip strength and mid-arm muscle area when compared to cholestatic disease. Conclusions: Child-Pugh class C is associated with greater early postoperative morbidity. Advanced Child-Pugh class is also associated with diminished muscle status and parenchymal disease.