Thermal Stability of Human Immunoglobulins with Sorbitol: A Critical Evaluation

The effect of the additive sorbitol on the thermal stabilization of human IgG was investigated by differential scanning calorimetry and size exclusion chromatography. In the presence of 33% sorbitol, the temperature at which denaturation of IgG began (T_i) was increased from 52 to 65°C. Similarly, the temperature of the maximum heat capacity (T_max) was increased from 69 to 76°C. Sorbitol also decreased dimer aggregation and the extent of oligomerization during heating compared with IgG dissolved in phosphate buffer. Sorbitol at 33% prevented massive protein denaturation but a 10–15% of oligomerization of high molecular weight aggregates with turbidity could not be avoided when heating for 10 h at 60°C. The use of sorbitol 33% to avoid heat denaturation of human IgG during viral inactivation did not prevent protein aggregation or the appearance of turbidity. Consequently, further processing will be required to achieve a product suitable for pharmaceutical use.     

Studies on the regulation of myocardial blood flow in man II. Effects of acute arterial hypoxia

To determine whether adjustment of myocardial blood flow (MBF), myocardial oxygen consumption (MVO₂) and myocardial substrate uptake (MSU) to acute arterial hypoxia is influenced by training effects on the heart, 7 trained and 7 untrained healthy individuals were investigated. MBF (argon method), MVO₂ and MSU of glucose, lactate and free fatty acids were measured at rest during normoxia and two different stages of acute arterial hypoxia: a) 12.82 vol% O₂; b) 8.74 vol% O₂. Measurements were carried out during hemodynamic and respiratory steady state conditions. Myocardial flow and metabolism of athletes were significantly (p<0.01) lower compared to untrained subjects. In the trained cohort, MBF increased from 65 ± 19 to 73 ± 16 (a) and 98 ± 23 (b) ml/min·100 g. MVO₂ remained at normoxic control level of 8.00 ± 2.27 ml/min·100g. In the untrained group, MBF increased from 77 ± 15 to 84 ± 20 (a) and 108 ± 18 (b) ml/min · 100g. Again, there was no significant deviation in MVO₂ from the normoxic level of 10.11 ± 1.90 ml/min·100g. Decrease in arterial oxygen content was overcompensated by an increase in coronary conductance resulting in a significantly improved efficiency of myocardial perfusion during severe hypoxia. MSU of glucose, lactate and free fatty acids as well as calculated ATP production did not change significantly during hypoxia. It is concluded that training effects on the heart do not influence regulation of MBF, MVO₂ and MSU during moderate or severe acute arterial hypoxia. Reaction of coronary smooth muscle tone to a decrease in oxygen partial pressure is independent from training effects. However, both acute arterial hypoxia and physical training exert synergetic effects on the heart by reducing myocardial oxygen consumption per heart beat. Thus, it is assumed that adaptive properties of myocardial blood flow and metaboüsm to severe hypoxia are more pronounced in trained than in untrained individuals.     

Systemic inhibition of spontaneous calcification by the serum protein alpha 2-HS glycoprotein/fetuin

The extracellular fluid is a metastable system with regard to calcium and phosphate ions. Active inhibitors of calcification must be present in serum to prevent the spontaneous formation of Ca2+.Pi solid phases which could otherwise precipitate to cause renal calcinosis and block small blood vessels. alpha 2-HS glycoproteins/fetuins, AHSGs, are ideal candidates for this function. AHSGs are ubiquitous and highly abundant in serum; they bind calcium and efficiently prevent de novo formation of apatitic mineral. Normocalcemic AHSG-deficient mice develop sporadic perivascular calcification. Hypercalcemia induced by dietary means or by hormone treatment results in lethal calcinosis in Ahsg-/-mice. A mineral binding structure is proposed for domain D1 of AHSG suggesting that the proposed EF-hand motif for calcium binding does not exist in AHSG. Unlike serum albumin, AHSG does not preferentially bind ionic Ca2+, but rather in the form of apatitic microcrystals.     

Association between the TAP1 gene polymorphisms and recurrent respiratory papillomatosis in patients from Western Mexico: A pilot study

BackgroundRecurrent respiratory papillomatosis (RRP) is a respiratory tract disease that affects children and adults and is characterized by the recurrent proliferation of multiple papillomas. The etiologic agent is the human papillomavirus, mainly genotypes 6 and 11. Furthermore, polymorphisms in TAP1 appear to influence the selection of antigenic peptides and the transport process to the rough endoplasmic reticulum, for their subsequent presentation to T lymphocytes, an essential process against viral diseases and tumor processes. Previous studies have shown that individuals with those polymorphisms are susceptible to immune, infectious, and tumor‐related diseases. The present study aimed to determine the association between the TAP1 rs1057141 (c.1177A>G) and rs1135216 (c.2090A>G) single nucleotide polymorphisms (SNPs) and RRP.MethodsA case–control study was carried out on a group of 70 individuals (35 controls and 35 patients). RRP diagnosis, HPV genotyping, and viral load were determined through histology and PCR. SNPs rs1057141 and rs1135216 were identified through allelic discrimination, using real‐time PCR. The haplotypic analyses were performed using the Arlequin 3.5 program.ResultsHPV‐6 and HPV‐11 were the genotypes found in the samples. In the polymorphism analysis, rs1057141 showed no significant differences (p = 0.049, CI = 0.994–7.331). In contrast, a significant difference was found in rs1135216 (p = 0.039, OR = 2.4) in the allelic analysis, as well as in the dominant (p = 0.027, OR = 3.06), codominant (p = 0.033, OR = 3.06), and additive model (p = 0.043, OR = 2.505) in subjects with the G allele.ConclusionThe G allele in rs1135216 was associated with a genetic risk of susceptibility for RRP in a population in Western Mexico.     

Novel ssDNA viruses discovered in yellow-crowned parakeet (Cyanoramphus auriceps) nesting material

During routine monitoring of yellow-crowned parakeets in the Poulter Valley of the South Island of New Zealand, a dead parakeet chick was discovered in a nest. Known parrot-infecting viruses, such as beak and feather disease virus (BFDV), avian polyomavirus (APV), and parrot hepatitis B virus (PHBV), were not detected in the nesting material. However, we recovered two novel single-stranded DNA viruses (ssDNA), CynNCXV (2308 nt) and CynNCKV (2087 nt), which have genome architectures similar to those of circoviruses, characterised by circular genomes with two large bidirectional open reading frames (ORFs). Both contain a stem-loop element with a conserved nonanucleotide motif, known to be required for rolling-circle replication. The full genomes had no BLASTn similarity to known ssDNA viruses. However, in both genomes the larger ORFs have BLAST similarity to known replication-associated proteins (Reps). CynNCKV has 30 % similarity to picobiliphyte nano-like virus (Picobiliphyte M5584-5) with 66-88 % coverage (e-value of 5×10^?33), whereas CynNCXV has 33 % similarity to rodent stool-associated virus (RodSCV M-45) with 92-94 % coverage (e-value of 5 × 10^?31). Found within these ORFs were the rolling-circle replication motifs I, II, III and the helicase motifs Walker A and Walker B. Maximum-likelihood phylogenetic analysis of the Reps reveals that these are two novel ssDNA viruses. At this point, we are unable to attribute the death of the parakeet to these two new novel ssDNA viruses.     

Beyond physiotherapy and pharmacological treatment for fibromyalgia syndrome: tailored tACS as a new therapeutic tool

European Archives of Psychiatry and Clinical Neuroscience - Fibromyalgia syndrome (FMS) is a complex pain disorder, characterized by diffuse pain and cognitive disturbances. Abnormal cortical...     

High microvessel density in pancreatic ductal adenocarcinoma is associated with high grade

The objectives of this work are to study angiogenesis in pancreatic ductal adenocarcinoma using computerized morphometric and image analysis and to compare the microvascular density in intratumoral and peritumoral areas and normal pancreatic tissue. Microvascular density was analyzed in 60 cases of pancreatic ductal adenocarcinoma and 30 samples of normal pancreatic tissue using an avidin–biotin immunoperoxidase technique with an anti-CD31 antibody. Microvascular density (MVD) was analyzed through digital microimaging and computerized analysis. The blood vessel density in the tumor was significantly higher than in peritumoral areas and in normal pancreatic tissue. Well differentiated pancreatic ductal adenocarcinomas contained higher MVD than poorly differentiated carcinomas. In pancreatic adenocarcinoma, MVD is higher than in peritumoral tissue or normal pancreatic tissue.     

Implications of combined ovariectomy and glucocorticoid (dexamethasone) treatment on mineral,microarchitectural, biomechanical and matrix properties of rat bone

Osteoporosis is one of the deleterious side effects of long-term glucocorticoid therapy. Since the condition is particularly aggressive in postmenopausal women who are on steroid therapy, in this study we have attempted to analyse the combined effect of glucocorticoid (dexamethasone) treatment and cessation of oestrogen on rat bone. The dual aim was to generate osteoporotic bone status in a short time scale and to characterise the combination of glucocorticoid–postmenopausal osteoporotic conditions. Sprague Dawley rats (N = 42) were grouped randomly into three groups: untreated control, sham-operated and ovariectomized–steroid (OVX-Steroid) rats. Control animals were euthanized with no treatment [Month 0 (M0)], while sham and OVX-Steroid rats were monitored up to 1 month (M1) and 3 months (M3) post laparotomy/post OVX-Steroid treatment. Histology, dual-energy X-ray absorptiometry (DXA), micro-computed tomography (micro-CT), and biomechanical and mRNA expression analysis of collagenous, non-collagenous matrix proteins and osteoclast markers were examined. The study indicated enhanced osteoclastogenesis and significantly lower bone mineral density (BMD) in the OVX-Steroid rats with Z-scores below −2.5, reduced torsional strength, reduced bone volume (BV/TV%), significantly enhanced trabecular separation (Tb.S), and less trabecular number (Tb.N) compared with sham rats. Osteoclast markers, cathepsin K and MMP 9 were upregulated along with Col1α1 and biglycan with no significant expression variation in fibronectin, MMP 14, LRP-5, Car II and TNC. These results show higher bone turnover with enhanced bone resorption accompanied with reduced torsional strength in OVX-Steroid rats; and these changes were attained within a short timeframe. This could be a useful model which mimics human postmenopausal osteoporosis that is associated with steroid therapy and could prove of value both in disease diagnosis and for testing generating and testing biological agents which could be used in treatment.     

Stability and marginal bone loss in implants placed using piezoelectric osteotomy versus conventional drilling: systematic review and meta-analysis

Background The main objective of this systematic review was to compare primary and secondary implant stability between placement with piezoelectric osteotomy and conventional drilling, comparing marginal bone losses as a secondary objective. Material and Methods An electronic search was conducted using PubMed (MEDLINE), Scopus, and Cochrane Library (Wiley) databases, besides a manual search. Results A total of 153 articles were retrieved, 39 from Pubmed, 44 from Scopus, and 70 from the Cochrane Library. After removing duplicates, 112 articles (1 from the manual search) were screened, and 9 were finally selected for qualitative and statistical analyses. Conclusions Piezoelectric surgery is a predictable alternative to conventional drilling for dental implant placement. Medium/long-term survival rates and marginal bone losses are similar between piezoelectric osteotomy and conventional drilling, and there is no difference in ISQ values for primary stability. However, implants placed with ultrasound showed a lower decrease in implant stability quotient (ISQ) during the osseointegration period and a higher ISQ value for secondary stability. This study contributes further information on peri-implant bone tissue at 3 and 6 months after implant placement with piezoelectric osteotomy or conventional drilling and provides an updated meta-analysis of comparative studies. Key words:Piezosurgery, piezoelectric surgery, conventional drill, implant site preparation, dental implant, implant stability, marginal bone loss.