Clonal types and multidrug resistance patterns of methicillin-resistant Staphylococcus aureus (MRSA) recovered in Italy during the 1990s

A large number (272) of methicillin-resistant Staphylococcus aureus (MRSA) isolates recovered from Italian hospitals during the early and late 1990s were characterized for multidrug resistance pattern and clonal type using a combination of genotyping methods, including pulsed-field gel electrophoresis (PFGE), spaA typing, multilocus sequence typing (MLST), determination of SCC mec type, and hybridization pattern with Tn 554. The majority of MRSA belonged to four genetic lineages: the pandemic Iberian and Brazilian clones, and two unique clonal types-the "Italian" and "Rome" clones of MRSA. The Italian clone carried the SCC mec type I in the genetic background of ST228, which is a double-locus variant of the sequence type of the multidrug-resistant New York/Japanese clone (ST5). The properties of the Rome clone showed several striking similarities to those of the Archaic clone of MRSA that was dominant among MRSA isolates in the mid-1960s to 1970s, but has not been detected since then in recent global surveillance studies.     

Complete HLA-B44 subtyping in Spaniards. Additional evidence for heterogeneity in Caucasian populations

HLA-B44 is one of the most common HLA class I alleles in Caucasians. Exon 3 oligotyping and sequence analysis have define five B44 subtypes: B^*4402, B^*4403, B^*4404, B^*4405 and B^*4406, with variations in exons 2 and 3. We have developed a conventional DNA typing system by using a single B12-group specific amplification including exon2-intron2-exon3 in combination with 6 oligoprobes to define all B44 subtypes. 140 HLA-B44 positive unrelated Spanish Caucasians were typed. Family studies established 30 B44-bearing haplotypes. The distribution of B44 subtypes in our population was: B^*4402 32.5%, B^*4403 66.5%, B^*4404 0.5%, B^*4405 0.5%, B^*4406 not found. B^*4402 and B^*4403 represented the 99% of the B44 alleles, as described in Caucasians. However, these two major subtypes showed an inverted frequency when compared with other Caucasian populations, B^*4403 twice as frequently as B^*4402 in Spaniards. HLA-B44-associated chromosomes showed 20 different haplotypes (including HLA-A,-C,-DR,-DQ), although demonstrating clear separated haplotype composition between B^*4402 and B^*4403: B^*4402 associated to class I alleles A2 ( ) and Cw5 ( ), and B^*4403 associated to the class II allele DRB1^*0701 ( ). These findings, in addition to the validation of a complete B44 oligotyping system, revealed further evidence of antigen frequency differences among populations of the same ethnic origin.     

Pregnancies after intracytoplasmic sperm injection with cryopreserved testicular spermatozoa

In 25 patients (14 suffering from obstructive azoospermia, sixfrom non-obstructive azoospermia, three from astheno-azoospermiaand two from absence of ejaculation) spermatozoa were extractedfrom testicular biopsies. Intracytoplasmic sperm injection (ICSI)with fresh testicular spermatozoa was performed in 18 cases;spermatozoa in excess were cryopreserved in pills. No pregnancieswere achieved. In the remaining seven patients, testicular spermatozoawere retrieved and cryopreserved during a diagnostic testicularbiopsy. After thawing, sperm motility was assessed in 17 cases(68%), and 18 ICSI with cryopreserved testicular spermatozoawere performed. The mean two-pronuclear (2PN) fertilizationrate was 59%, the mean cleavage rate was 92%, and six clinicalpregnancies were achieved, all of them still ongoing (pregnancyrate 33%). A comparison of the results of ICSI carried out withfresh or cryopreserved testicular spermatozoa showed that themean 2PN fertilization rates per cycle (53 compared with 55%),mean cleavage rates per cycle (99 compared with 96%) and embryoquality were not significantly different In conclusion, cryopreservationof testicular spermatozoa is feasible, even in patients withnon-obstructive azoospermia, and the results of ICSI with frozen-thawedtesticular spermatozoa are similar to those obtained using freshtesticular spermatozoa. Cryopreservation of testicular spermatozoamay avoid repetition of testicular biopsies to retrieve spermatozoafor successive ICSI cycles in patients in whom the only sourceof motile spermatozoa is the testicle.     

Pulmonary and mediastinal "sarcoidosis" following surgical resection of cancer

Previous reports indicate that enlarged hilar and mediastinal lymph nodes caused by sarcoid-like reactions may develop after curative resection of cancer, and their presence does not necessarily denote neoplastic recurrence. Reports further suggest that coexisting pulmonary infiltrates in this setting may be related to sarcoidosis. In this study, we describe two patients who had resected lung and gastric cancer and who later developed pulmonary interstitial infiltrate, concurrent with progressive mediastinal lymphadenopathy initially thought to be caused by intrathoracic dissemination of their cancer. These changes were shown by open lung biopsy to be a benign, granulomatous reaction interpreted as sarcoidosis. Thus, it is important to recognize this clinical pattern when pulmonary infiltrates develop after complete treatment of cancer in an otherwise relapse-free patient and to encourage lung or lymph node biopsy in these particular settings in order to confirm a sarcoid-like reaction, thereby avoiding unnecessary chemotherapy for presumed tumor recurrence.     

Histamine stimulates neurogenesis in the rodent subventricular zone

Neural stem/progenitor cells present in the subventricular zone (SVZ) are a potential source of repairing cells after injury. Therefore, the identification of novel players that modulate neural stem cells differentiation can have a huge impact in stem cell-based therapies. Herein, we describe a unique role of histamine in inducing functional neuronal differentiation from cultured mouse SVZ stem/progenitor cells. This proneurogenic effect depends on histamine 1 receptor activation and involves epigenetic modifications and increased expression of Mash1, Dlx2, and Ngn1 genes. Biocompatible poly (lactic-co-glycolic acid) microparticles, engineered to release histamine in a controlled and prolonged manner, also triggered robust neuronal differentiation in vitro. Preconditioning with histamine-loaded microparticles facilitated neuronal differentiation of SVZ-GFP cells grafted in hippocampal slices and in in vivo rodent brain. We propose that neuronal commitment triggered by histamine per se or released from biomaterial-derived vehicles may represent a new tool for brain repair strategies. STEM CELLS 2012; 30:773-784.     

Decreased humoral antibody episodes of acute renal allograft rejection in recipients expressing the HLA-DQβ1*0202 allele

The present investigation was designed to show the effect of human leukocyte antigen (HLA) class II molecular allelic specificities in the recipient on the induction of humoral antibody rejection, identified by C4d peritubular capillary staining, as well as specific antibody identified by Luminex technology. Major histocompatibility complex (MHC) class II molecules are expressed on dendritic cells, macrophages, and B lymphocytes and they present antigenic peptides to CD4 positive T lymphocytes. Human renal peritubular and glomerular capillaries express class II MHC molecules upon activation. Expression of class II molecules on renal microvascular endothelial cells exposes them to possible interaction with specific circulating antibodies. We hypothesize that HLA-DQβ1*0202 expression in recipients decreases the likelihood of antibody-mediated renal allograft rejection. We found that 80% (=25) of DQ2 positive haplotype recipients failed to induce humoral antibody renal allograft rejection and 20% (n=25) of DQ2 positive haplotype recipients induced humoral antibody renal allograft rejection (p=0.008). By contrast, 48% (n=46) of DQ2 negative haplotype recipients failed to induce a humoral antibody component of renal allograft rejection and 52% (n=46) of DQ2 negative haplotype recipients induced humoral antibody-mediated renal allograft rejection. Our results suggest that recipients who express the DQβ1*0202 allele are less likely to induce a humoral antibody component of acute renal allograft rejection than are those expressing DQ1, DQ3, or DQ4 alleles. DQβ1*0202 allele expression in recipients could possibly be protective against acute humoral allograft rejection and might serve as a future criterion in recipient selection and in appropriate therapy for acute renal rejection episodes.     

The influence of physical activity in the progression of experimental lung cancer in mice

Lung cancer is one of the most incident neoplasms in the world, representing the main cause of mortality for cancer. Many epidemiologic studies have suggested that physical activity may reduce the risk of lung cancer, other works evaluate the effectiveness of the use of the physical activity in the suppression, remission and reduction of the recurrence of tumors. The aim of this study was to evaluate the effects of aerobic and anaerobic physical activity in the development and the progression of lung cancer. Lung tumors were induced with a dose of 3mg of urethane/kg, in 67 male Balb - C type mice, divided in three groups: group 1_24 mice treated with urethane and without physical activity; group 2_25 mice with urethane and subjected to aerobic swimming free exercise; group 3_18 mice with urethane, subjected to anaerobic swimming exercise with gradual loading 5-20% of body weight. All the animals were sacrificed after 20 weeks, and lung lesions were analyzed. The median number of lesions (nodules and hyperplasia) was 3.0 for group 1, 2.0 for group 2 and 1.5-3 (p=0.052). When comparing only the presence or absence of lesion, there was a decrease in the number of lesions in group 3 as compared with group 1 (p=0.03) but not in relation to group 2. There were no metastases or other changes in other organs. The anaerobic physical activity, but not aerobic, diminishes the incidence of experimental lung tumors.     

Swim training does not protect mice from skeletal muscle oxidative damage following a maximum exercise test

We investigated whether swim training protects skeletal muscle from oxidative damage in response to a maximum progressive exercise. First, we investigated the effect of swim training on the activities of the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), in the gastrocnemius muscle of C57Bl/6 mice, 48 h after the last training session. Mice swam for 90 min, twice a day, for 5 weeks at 31°C (± 1°C). The activities of SOD and CAT were increased in trained mice (P < 0.05) compared to untrained group. However, no effect of training was observed in the activity of GPx. In a second experiment, trained and untrained mice were submitted to a maximum progressive swim test. Compared to control mice (untrained, not acutely exercised), malondialdehyde (MDA) levels were increased in the skeletal muscle of both trained and untrained mice after maximum swim. The activity of GPx was increased in the skeletal muscle of both trained and untrained mice, while SOD activity was increased only in trained mice after maximum swimming. CAT activity was increased only in the untrained compared to the control group. Although the trained mice showed increased activity of citrate synthase in skeletal muscle, swim performance was not different compared to untrained mice. Our results show an imbalance in the activities of SOD, CAT and GPx in response to swim training, which could account for the oxidative damage observed in the skeletal muscle of trained mice in response to maximum swim, resulting in the absence of improved exercise performance.     

Histopathological features of keratocystic odontogenic tumor: a descriptive study of 177 cases from a Brazilian population

The aim of this study was to describe the clinicopathologic features of 177 keratocystic odontogenic tumors (KCOTs) diagnosed in a Brazilian population. A total of 177 KCOTs were reviewed and affected 158 patients with ages ranging from 5 to 79 years (mean age = 32 years) with a slight female predominance. Mandible was the most common affected site (69.3%), and a unilocular radiolucency was the most common radiographic image. Microscopically, all cases showed at least focal areas of classic KCOT, but several histological aspects were also observed, including diffuse and focal epithelial lining hyperplasia (48.6%), epithelial budding (12.4%), reactive cytological alterations (11.3%), dystrophic calcification (7.9%), daughter cysts (7.8%), odontogenic epithelial remnants (4.5%), focal areas of orthokeratinization (2.8%), and ameloblastomatous epithelium (1.7%). These variations may make KCOT diagnosis challenging in some cases, so careful full-sample analysis and knowledge of these uncommon histological features associated with KCOT are essential for correct diagnosis.     

Toll-like receptor signal adaptor protein MyD88 is required for sustained endotoxin-induced acute hypoferremic response in mice

Hypoferremia, associated with immune system activation, involves a marked reduction in the levels of circulating iron, coupled with iron sequestration within macrophages. Toll-like receptor (TLR) signaling plays an important role in the development of the hypoferremic response, but how downstream signaling events affect genes involved in iron metabolism is incompletely understood. We investigated the involvement of MyD88-dependent (MyD88) and MyD88-independent (TRIF) TLR signaling in the development of hypoferremia. Using MyD88-deficient and TRIF-deficient mice, we show that MyD88 and TRIF signaling pathways are critical for up-regulation by lipopolysaccharide (LPS) of the iron regulator hepcidin. In addition, MyD88 signaling is required for the induction of lipocalin 2 secretion and iron sequestration in the spleen. Activation of TLR4 and TLR3 signaling through LPS and polyinosinic:polycytidylic acid [poly(I:C)] treatments resulted in rapid down-regulation of HFE protein [encoded by the hemochromatosis gene (Hfe)] and ferroportin [encoded by solute carrier family 40 (iron-regulated transporter), member 1 (Slc40a1)] expression in the spleen, independent of MyD88 or TRIF signaling and proinflammatory cytokine production. However, lack of MyD88 signaling significantly impaired the hypoferremic response triggered by LPS, indicating that ferroportin and HFE protein down-regulation alone are insufficient to maintain hypoferremia. The extent of the hypoferremic response was found to be limited by initial, basal iron levels. Together, these results suggest that targeting specific TLR signaling pathways by affecting the function of adaptor molecules may provide new strategies to counteract iron sequestration within macrophages during inflammation.