Recently, a new classification for gastric cancer (GC) has been proposed, based on Lauren's histology and on anatomic tumour location, identifying three subtypes of disease: type 1 (proximal non diffuse GC), type 2 (diffuse GC) and type 3 (distal non diffuse GC). Aim of our analysis was to compare clinical outcome according to different GC subtypes (1,2,3) in metastatic GC patients receiving first-line chemotherapy.
Patients and Methods
Advanced GC pts treated with a first-line combination chemotherapy were included in our analysis. Pts were divided in three subgroups (type 1, type 2 and type 3) as previously defined.
A total of 248 advanced GC pts were included: 45.2% belonged to type 2, 43.6% to type 3 and 11.2% to type 1. Patients received a fluoropyrimidine-based chemotherapy doublet or three drugs regimens including a platinum derivate and a fluoropyrimidine with the addition of an anthracycline, a taxane or mytomicin C. RR was higher in type 1 pts (RR = 46.1%) and type 3 (34,3%) compared to type 2 (20,4%), (p = 0.015). Type 2 presented a shorter PFS, median PFS = 4.2 months, compared to type 1, mPFS = 7.2 months, and type 3, mPFS = 5.9 months (p = 0.011) and also a shorter OS (p = 0.022).
Our analysis suggests that GC subtypes may be important predictors of benefit from chemotherapy in advanced GC patients. Future clinical trials should take in account these differences for a better stratification of patients.
Simian immunodeficiency virus (SIV) stocks for in vivo nonhuman primate models of AIDS are typically generated by transfection of 293T cells with molecularly cloned viral genomes or by expansion in productively infected T cells. Although titers of stocks are determined for infectivity in vitro prior to in vivo inoculation, virus production methods may differentially affect stock features that are not routinely analyzed but may impact in vivo infectivity, mucosal transmissibility, and early infection events. We performed a detailed analysis of nine SIV stocks, comprising five infection-derived SIVmac251 viral swarm stocks and paired infection- and transfected-293T-cell-derived stocks of both SIVmac239 and SIVmac766. Representative stocks were evaluated for (i) virus content, (ii) infectious titer, (iii) sequence diversity and polymorphism frequency by single-genome amplification and 454 pyrosequencing, (iv) virion-associated Env content, and (v) cytokine and chemokine content by 36-plex Luminex analysis. Regardless of production method, all stocks had comparable particle/infectivity ratios, with the transfected-293T stocks possessing the highest overall virus content and infectivity titers despite containing markedly lower levels of virion-associated Env than infection-derived viruses. Transfected-293T stocks also contained fewer and lower levels of cytokines and chemokines than infection-derived stocks, which had elevated levels of multiple analytes, with substantial variability among stocks. Sequencing of the infection-derived SIVmac251 stocks revealed variable levels of viral diversity between stocks, with evidence of stock-specific selection and expansion of unique viral lineages. These analyses suggest that there may be underappreciated features of SIV in vivo challenge stocks with the potential to impact early infection events, which may merit consideration when selecting virus stocks for in vivo studies.
Absence epilepsy is generated by the cortico-thalamo-cortical network, which undergoes a finely tuned regulation by metabotropic glutamate (mGlu) receptors. We have shown previously that potentiation of mGlu1 receptors reduces spontaneous occurring spike and wave discharges (SWDs) in the WAG/Rij rat model of absence epilepsy, whereas activation of mGlu2/3 and mGlu4 receptors produces the opposite effect. Here, we have extended the study to mGlu5 receptors, which are known to be highly expressed within the cortico-thalamo-cortical network. We used presymptomatic and symptomatic WAG/Rij rats and aged-matched ACI rats. WAG/Rij rats showed a reduction in the mGlu5 receptor protein levels and in the mGlu5-receptor mediated stimulation of polyphosphoinositide hydrolysis in the ventrobasal thalamus, whereas the expression of mGlu5 receptors was increased in the somatosensory cortex. Interestingly, these changes preceded the onset of the epileptic phenotype, being already visible in pre-symptomatic WAG/Rij rats. SWDs in symptomatic WAG/Rij rats were not influenced by pharmacological blockade of mGlu5 receptors with MTEP (10 or 30 mg/kg, i.p.), but were significantly decreased by mGlu5 receptor potentiation with the novel enhancer, VU0360172 (3 or 10 mg/kg, s.c.), without affecting motor behaviour. The effect of VU0360172 was prevented by co-treatment with MTEP. These findings suggest that changes in mGlu5 receptors might lie at the core of the absence-seizure prone phenotype of WAG/Rij rats, and that mGlu5 receptor enhancers are potential candidates to the treatment of absence epilepsy.
Absence epilepsy; WAG/Rij rats; mGlu5 receptor; VU0360172; MTEP
A variant upstream of human leukocyte antigen C (HLA-C) shows the most significant genome-wide effect on HIV control in European Americans and is also associated with the level of HLA-C expression. We characterized the differential cell surface expression levels of all common HLA-C allotypes and tested directly for effects of HLA-C expression on outcomes of HIV infection in 5243 individuals. Increasing HLA-C expression was associated with protection against multiple outcomes independently of individual HLA allelic effects in both African and European Americans, regardless of their distinct HLA-C frequencies and linkage relationships with HLA-B and HLA-A. Higher HLA-C expression was correlated with increased likelihood of cytotoxic T lymphocyte responses and frequency of viral escape mutation. In contrast, high HLA-C expression had a deleterious effect in Crohn’s disease, suggesting a broader influence of HLA expression levels in human disease.
Clinical data indicate that prognostic stratification of radically resected colorectal cancer based on disease stage only may not be always be adequate. Preclinical findings suggest that cancer stem cells may influence the biological behaviour of colorectal cancer independently from stage: objective of the study was to assess whether a panel of stemness markers were correlated with clinical outcome in resected stage II and III colon cancer patients. A panel of 66 markers of stemness were analysed and thus patients were divided into two groups (A and B) with most patients clustering in a manner consistent with different time to relapse by using a statistical algorithm. A total of 62 patients were analysed. Thirty-six (58%) relapsed during the follow-up period (range 1.63–86.5 months). Twelve (19%) and 50 (81%) patients were allocated into group A and B, respectively. A significantly different median relapse-free survival was observed between the 2 groups (22.18 vs 42.85 months, p = 0.0296). Among of all genes tested, those with the higher “weight” in determining different prognosis were CD44, ALCAM, DTX2, HSPA9, CCNA2, PDX1, MYST1, COL1A1 and ABCG2. This analysis supports the idea that, other than stage, biological variables, such as expression levels of colon cancer stem cell genes, may be relevant in determining an increased risk of relapse in resected colorectal cancer patients.
Acanthamoeba keratitis is a rare but serious corneal disease, often observed in contact lens wearers. Clinical treatment of infected patients frequently involves the use of polyhexamethylene biguanide (PHMB), a polymer used as a disinfectant and antiseptic, which is toxic also for the epithelial cells of the cornea. Prompt and effective diagnostic tools are hence highly desiderable for both starting early therapy and timely suspension of the treatment. In this work we use Raman microspectroscopy to analyse in vitro a single Acanthamoeba cell in cystic phase. In particular, we investigate the effect of PHMB at the single-cell level, providing useful information on both the underlying biochemical mechanism and the time frame for Acanthamoeba eradication in ocular infections. Furthermore, we demonstrate that Raman spectroscopy, in conjunction with standard multivariate analysis methods, allows discriminating between live and dead Acanthamoebas, which is fundamental to optimizing patients’ treatment.
Wiskott-Aldrich Syndrome protein (WASp)–mediated actin polymerization controls intracellular trafficking and compartmentalization of TLR9 ligands in plasmacytoid dendritic cells.
Mutations in Wiskott-Aldrich syndrome (WAS) protein (WASp), a regulator of actin dynamics in hematopoietic cells, cause WAS, an X-linked primary immunodeficiency characterized by recurrent infections and a marked predisposition to develop autoimmune disorders. The mechanisms that link actin alterations to the autoimmune phenotype are still poorly understood. We show that chronic activation of plasmacytoid dendritic cells (pDCs) and elevated type-I interferon (IFN) levels play a role in WAS autoimmunity. WAS patients display increased expression of type-I IFN genes and their inducible targets, alteration in pDCs numbers, and hyperresponsiveness to TLR9. Importantly, ablating IFN-I signaling in WASp null mice rescued chronic activation of conventional DCs, splenomegaly, and colitis. Using WASp-deficient mice, we demonstrated that WASp null pDCs are intrinsically more responsive to multimeric agonist of TLR9 and constitutively secrete type-I IFN but become progressively tolerant to further stimulation. By acute silencing of WASp and actin inhibitors, we show that WASp-mediated actin polymerization controls intracellular trafficking and compartmentalization of TLR9 ligands in pDCs restraining exaggerated activation of the TLR9–IFN-α pathway. Together, these data highlight the role of actin dynamics in pDC innate functions and imply the pDC–IFN-α axis as a player in the onset of autoimmune phenomena in WAS disease.
The purpose of this study is to report a case of full-arch rehabilitation on six endosseous implants loaded following the standard procedure.
An implant-prosthetic treatment was proposed to a 53-year-old woman with a total prosthesis in the upper jaw. Six implants on upper maxillary were placed keeping the upper complete denture during the osseointegration period. The implants were left submerged to allow the patient to wear removable prostheses and the prosthesis was rebase with Hydrocast to not compress the sites of healing during the osseointegration period.
The impression of implants was made with silicones for addition (VPS) with different viscosities after 8 weeks.
The final restoration was carried out taking into account the aesthetic and functional canons.
Correct diagnosis and accurate implant planning are key for success in implant rehabilitation.
full-arch rehabilitation; VDO; implant supported prosthesis
Lymphoepithelioma is a very rare form of malignant tumor originating from epithelial line cells. Its occurrence has potential clinical, therapeutic and prognostic implications. In the present report we describe an unusual case of bladder cancer with two different histological varieties: transition cell carcinoma and lymphoepithelioma-like carcinoma. Lymphoepithelioma-like carcinoma of the bladder has only been rarely reported in the literature to date.
We present the case of a 68-year-old Caucasian man who, after occurrence of hematuria, underwent transurethral resection of a bladder tumor. The results of a histological examination confirmed a high-grade non-muscle-invasive pT1 lymphoepithelioma-like carcinoma of the urinary bladder, associated with a concurrent high-grade transition cell carcinoma. After analyzing the histological features, our patient was subjected to treatment with intra-vesical instillations of bacillus Calmette-Guérin. Our work stresses that diagnosis and therapeutic approaches can be difficult and controversial, especially in the early stages of this rare carcinoma.
This report emphasizes the importance of extending our knowledge and experiences regarding this uncommon carcinoma. Further studies are needed to better understand this rare disease and define more accurate diagnostic and therapeutic strategies.
Bacillus Calmette-Guérin Instillations; Lymphoepithelioma-like Carcinoma; Urinary Bladder
Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency caused by the defective expression of the WAS protein (WASP) in hematopoietic cells. It has been shown that dendritic cells (DCs) are functionally impaired in WAS patients and was−/− mice. We have previously demonstrated the efficacy and safety of a murine model of WAS gene therapy (GT), using stem cells transduced with a lentiviral vector. The aim of this study was to investigate whether GT can correct DC defects in was−/− mice. As DCs expressing WASP were detected in the secondary lymphoid organs of the treated mice, we tested the in vitro and in vivo function of bone marrow-derived DCs (BMDCs). The BMDCs showed efficient in vitro uptake of latex beads and Salmonella typhimurium. When BMDCs from the treated mice (GT BMDCs) and the was−/− mice were injected into wild type hosts, we found a higher number of cells that had migrated to the draining lymph nodes compared to mice injected with was−/− BMDCs. Finally, we found that OVA-pulsed GT BMDCs or vaccination with anti-DEC205 OVA fusion protein can efficiently induce antigen-specific T cell activation in vivo. These findings show that WAS GT significantly improves DC function, thus adding new evidence of the preclinical efficacy of lentiviral vector-mediated WAS GT.
Wiskott-Aldrich syndrome; Gene therapy; Dendritic cells
Obesity is considered an emerging epidemic that is often associated with non-alcoholic fatty liver disease. Among the therapeutic options for morbid obesity, bariatric surgery plays an important role when conventional therapies fail. The effects of bariatric surgery on liver function and morphology are controversial in the literature. Liver failure has been reported after jejunoileal bypass (JIB), biliopancreatic diversion and gastric bypass. Biliointestinal bypass (BIB) is considered an effective procedure among recently introduced bariatric surgery techniques. It is a clinically safe, purely malabsorptive operation in which the blind intestinal loop of the JIB is anastomosed to the gallbladder, allowing a portion of bile to transit into excluded intestinal tract. BIB is the only procedure, to our knowledge, to have no liver side effects reported in the literature. We report the case of a young obese woman who developed liver failure 8 mo after BIB. She had a rapid weight loss (70 kg) with a reduction in body mass index of 41% from January to September 2012. Because of a severe hepatic decompensation, she was referred to a transplantation centre. We strongly believe that the most important pathogenetic mechanism involved in the development of liver injury is the rapid weight loss that produced a significant fatty liver infiltration.
Bariatric surgery; Biliointestinal bypass; Liver failure; Non-alcoholic fatty liver disease; Obesity; Rapid weight loss
Development of patient-based questionnaire about aesthetic and functional differences between overdentures implant-supported and overdentures tooth-supported. Study of 43 patients with a follow up of 1 year.
The aim of this study is to compare functional efficiency and patients satisfaction between tooth-supported and implant-supported overdenture through a questionnaire that accurately reflects the real concerns of patients with dental prosthesis.
Forty-three patients were selected from the out patient clinic, Department of Dentistry “Fra G.B. Orsenigo Ospedale San Pietro F.B.F.”, Rome, Italy. Their age were ranging from 61 to 83 years. Eighteen patients were rehabilitated with overdentures supported by natural teeth and twenty-five with overdentures implant-supported.
Discussion and Result
The questionnaire proposed one year after the insertion of the prosthetis has showed that there isn’t difference statistically significant in terms of function, phonetics and aesthetics between overdenture implant-supported and tooth-supported.
The results of the questionnaire showed that the patients generally had a high level of satisfaction concern to the masticatory function, esthetics and phonetics. In addition, on average, they haven’t difficulty in removal and insertion of the denture and in oral hygiene. They haven’t in both groups problems related to fractures.
overdenture; prosthethic reabilitation; questionnaire
The object of this study was to develop an in vitro bioengineered three-dimensional vascularized skeletal muscle tissue, named eX-vivo Muscle Engineered Tissue (X-MET). This new tissue contains cells that exhibit the characteristics of differentiated myotubes, with organized contractile machinery, undifferentiated cells, and vascular cells capable of forming "vessel-like" networks. X-MET showed biomechanical properties comparable with that of adult skeletal muscles; thus it more closely mimics the cellular complexity typical of in vivo muscle tissue than myogenic cells cultured in standard monolayer conditions. Transplanted X-MET was able to mimic the activity of the excided EDL muscle, restoring the functionality of the damaged muscle. Our results suggest that X-MET is an ideal in vitro 3D muscle model that can be employed to repair muscle defects in vivo and to perform in vitro studies, limiting the use of live animals.
To assess the efficacy and safety of laser-assisted
percutaneous coronary interventions (PCI) in an unselected population.
One hundred consecutive patients, who underwent a laser
assisted PCI between January 2008 and March 2012, were included in the present study.
Fifty-one patients underwent laser ablation for thrombus vaporization (Group 1), 36
patients for neointima/plaque debulking (Group 2) and 13 patients for lesion compliance
modification in calcified lesions (Group 3).
The rate of
in-hospital serious events was 2%. The cumulative laser success was 82%, and it was
significantly higher for Group 1 and Group 2 in comparison with Group 3
(p = 0.001). Furthermore, the need for repeat revascularization was
significantly higher in the Group 3 compared with the others two groups (46% vs. 8% for
Group 1 and 11% for Group 2, p = 0.03). The MACE rate was 14%. There was
a trend toward a higher MACE rate in the Group 3 compared with others two groups
(p = 0.05).
Laser ablation is an
effective and safe tool for complex PCI. Patients underwent laser for thrombus
vaporization or for neointima/plaque debulking had better immediate success and better
outcome at follow-up than patients underwent laser for lesion compliance modification.
excimer laser; percutaneous transluminal coronary angioplasty; stents
Lactate dehydrogenase (LDH) represents a predictive factor in colorectal cancer patients treated with the angiogenesis inhibitor PTK/ZK. We explored the role of pre-treatment LDH serum levels in colorectal cancer patients receiving first-line bevacizumab.
Metastatic colorectal cancer treated with first-line bevacizumab was eligible. A control group including all consecutive patients treated with chemotherapy alone was also considered. Pre-treatment LDH serum levels were collected for all cases.
Median progression-free survival (PFS) in the control group for patients with high and low LDH levels was 4.2 and 8 months, respectively (P=0.0003). Median overall survival (OS) was 19.6 and 34.9 months for patients with high and low LDH levels, respectively (P=0.0014). In the bevacizumab group, partial responses were seen in 14 (58%) high-LDH and 8 (14%) low-LDH patients (P=0.0243), respectively, median PFS was 7.3 and 8.5 months, respectively (P=0.2), and median OS was 22 and 26.6 months, respectively (P=0.7).
High LDH levels correlated with worse prognosis. Bevacizumab seemed capable of improving clinical outcome in this specific group of patients who usually present with an adverse natural history. The improved response rate also suggests a role for LDH as a predictive marker.
bevacizumab; colorectal cancer; LDH; predictive factors
In Alzheimer disease (AD), the perturbation of the endoplasmic reticulum (ER) calcium (Ca2+) homeostasis has been linked to presenilins (PS), the catalytic core in γ-secretase complexes cleaving the amyloid precursor protein (APP) thereby generating amyloid-β (Aβ) peptides. Here we investigate whether APP contributes to ER Ca2+ homeostasis and whether ER Ca2+ could in turn influence Aβ production. We show that overexpression of wild-type human APP (APP695), or APP harboring the Swedish double mutation (APPswe) triggers increased Ryanodine receptors (RyR) expression and enhances RyR-mediated ER Ca2+ release in SH-SY5Y neuroblastoma cells and in APPswe-expressing (Tg2576) mice. Interestingly, dantrolene-induced lowering of RyR-mediated Ca2+ release leads to the reduction of both intracellular and extracellular Aβ load in neuroblastoma cells as well as in primary cultured neurons derived from Tg2576 mice. This Aβ reduction can be accounted for by decreased Thr-668-dependent APP phosphorylation and β- and γ-secretases activities. Importantly, dantrolene diminishes Aβ load, reduces Aβ-related histological lesions and slows down learning and memory deficits in Tg2576 mice. Overall, our data document a key role of RyR in Aβ production and learning and memory performances, and delineate RyR-mediated control of Ca2+ homeostasis as a physiological paradigm that could be targeted for innovative therapeutic approaches.
CCR5 is a main co-receptor for HIV, but also homes lymphocytes to sites of inflammation. We hypothesized that inhibition of CCR5 signaling would reduce HIV-associated chronic immune activation.
To test this hypothesis, we administered an antagonistic anti-CCR5 monoclonal antibody (HGS101) to five uninfected rhesus macaques (RMs) and monitored lymphocyte dynamics in blood and tissue.
CCR5 blockade resulted in decreased levels of CCR5+ T-cells in blood and, at later timepoints, in lymph nodes. Additionally, the levels of CD25+ T-cells increased in lymph nodes, but decreased in blood, bone marrow, and rectal mucosa. Finally, a profile of gene expression from HGS101-treated RMs revealed a subtle, but consistent, in vivo signature of CCR5 blockade that suggests a mild immune modulatory effect.
Treatment with anti-CCR5 antibody induces changes in the tissue distribution of CCR5+ and CD25+ T-cells that may impact on the overall levels of immune activation during HIV and SIV infection.
immune activation; trafficking; HIV
Ewing Sarcoma Family Tumours (ESFT) are rare in early childhood. The aim of this study was to report the clinical characteristics and outcome of children under 6 years of age affected by ESFT of the bone in Italy.
The records of all the children diagnosed with osseous ESFT in centres members of the Associazione Italiana di Ematologia ed Oncologia Pediatrica (AIEOP) from 1990 to 2008 were reviewed. The Kaplan–Meier method was used for estimating overall and progression-free survival (OS, PFS) curves; multivariate analyses were performed using Cox proportional hazards regression model.
This study includes 62 patients. An axial primary localization was present in 66% of patients, with the primary site in the chest wall in 34%. Fourteen (23%) patients presented metastatic disease. The 5-year OS and PFS were 73% (95% confidence interval, CI, 58–83%) and 72% (95% CI 57–83%) for patients with localized disease and 38% (95% CI 17–60%) and 21% (95% CI 5–45%) for patients with metastatic disease. Metastatic spread, skull/pelvis/spine primary localization, progression during treatment and no surgery predicted worse survival (P<0.01), while patients treated in the last decade had better survival (P = 0.002). In fact, the 5-year OS and PFS for patients diagnosed in the period 2000–2008 were 89% (95% CI 71–96%) and 86% (95% CI 66–94%), respectively.
The axial localization is the most common site of ESFT in pre-scholar children. Patients treated in the most recent period have an excellent outcome.
The aim of this study was the rapid identification of blaKPC gene in 38 Klebsiella pneumoniae clinical isolates with reduced susceptibility to carbapenems. The modified Hodge Test (MHT) was carried out to phenotypically determine whether resistance to carbapenems was mediated by a carbapenemase. The detection of the blaKPC gene was performed by real-time acid nucleic sequence-based amplification (NASBA™™), specifically designed for the detection of KPC RNA target.
Thirty-two/38 isolates evaluated by MHT showed the production of carbapenemases, while all the strains exhibited the production of KPC by inhibition test with phenylboronic acid (the combined disk test with IPM/IPM plus phenylboronic acid). The detection of blaKPC gene by Nuclisens EasyQ KPC yielded positive results in 38/38 (100%) strains. The presence of blaKPC gene was confirmed in all K. pneumoniae isolates when tested by the gold standard PCR assay.
In consideration of the serious challenge represented by infections due to K. pneumoniae it appears necessary the rapid identification of carbapenemases in clinical settings as it is made possible by the use of NASBA™ assay.
Klebsiella pneumoniae; Carbapenem resistance; blaKPC; NASBA™
Osteoarthritis of the hip is a common pathology and involves forms of disability and need for treatments that affect the quality of life of patients and their families, and in general of the whole society. It should be considered as such degenerative joint disease is increasing as the increase in life expectancy and musculoskeletal trauma, the latter responsible for secondary forms of osteoarthritis. The treatment of osteoarthritis of the hip has changed a lot over the years, since the earlier diagnosis and, before, with prevention through proper lifestyle. More in-depth knowledge of the biology of the tissues involved, first of all hyaline cartilage, has lead to non-surgical treatments such as infiltration with hyaluronic acid (viscosupplementation) and autologous growth factors derived from platelets (platelet rich plasma). Surgical therapy with prosthetic replacement is finally a choice to share with the patient based on pain and functional limitation, bearing in mind always the best technology and tribology and the possibility of less invasive surgical access, while recognizing that there are not still eternal prosthesis. Of particular importance then is the age of the patient. There are also other types of surgery (hip arthroscopy, forage) for other pathologies of the hip which can be resolutive, or, in a sense, can delay the arrival to the prosthetic replacement. We will discuss below the decision-making process that leads the surgeon with the patient to the surgery option.
hip arthrosis; hip arthroplasty; viscosupplementation; growth factors
Prosthetic-restorative approach for the restoration of tooth wear. Case report
This article presents a case report of combined prosthetic-adhesive rehabilitation in a patient with a generalized tooth wear.
A combined treatment adhesive - prosthetic was proposed to a male patient of 65 years old having a clinically significant tooth wear, with dentine exposure and with a reduction in clinical crown height. The erosive/abrasive worn dentition have been reconstructed with direct resin composite restorations on the posterior teeth and with zirconia crown on the anterior teeth.
Direct composite restorations have a number of distinct advantages. These restorations have proved durable and aesthetic, protect tooth structure and posterior occlusal contact is predictably re-established.
A combinations of direct and indirect restorations, based on the new vertical dimension of occlusion (VDO), can help to reestablish anatomy and function.
VDO; tooth wear; resin restoration; full-mouth rehabilitation
Using the diode laser in the lower labial frenum removal.
The aim of this study is to assess the advantages of the use of diode laser to removal inferior labial frenum.
The treatment with the diode laser was proposed to a female patient of 32 years old in good general health having an abnormal inferior labial frenum that causes retracting of the gingival margin. The incision was carried out with diode laser at a wavelength of 940 nm and was removed the frenum mucosa and the deep tissue constitute of connective fiber and muscle fiber. Before the surgery wasn’t used the local anesthetic and after the cutting wasn’t necessary the use of suture.
The wound had a good healing without scar. The patient didn’t have pain and bleeding during the healing and she didn’t report complications. It wasn’t necessary the use of antibiotic and anti-inflammatory.
The use of lasers has proved effective in the removal of labial frenum because it offers several advantages for the patient than traditional surgery.
diode laser; frenectomy; labial frenum; gingival retraction
Although currently available IGRA have been reported to be promising markers for TB infection, they cannot distinguish active tuberculosis (TB) from latent infection (LTBI).
Children with LTBI, active TB disease or uninfected were prospectively evaluated by an in-house ELISPOT assay in order to investigate possible immunological markers for a differential diagnosis between LTBI and active TB.
Children at risk for TB infection prospectively enrolled in our infectious disease unit were evaluated by in-house IFN-γ and IL-2 based ELISPOT assays using a panel of Mycobacterium tuberculosis antigens.
Twenty-nine children were classified as uninfected, 21 as LTBI and 25 as active TB cases (including 5 definite and 20 probable cases). Significantly higher IFN-γ ELISPOT responses were observed in infected vs. uninfected children for ESAT-6 (p<0.0001), CFP-10 (p<0.0001), TB 10.3 (p = 0.003), and AlaDH (p = 0.001), while differences were not significant considering Ag85B (p = 0.063), PstS1 (p = 0.512), and HspX (16 kDa) (p = 0.139). IL-2 ELISPOT assay responses were different for ESAT-6 (p<0.0001), CFP-10 (p<0.0001), TB 10.3 (p<0.0001), HspX (16 kDa) (p<0.0001), PstS1 (p<0.0001) and AlaDH (p = 0.001); but not for Ag85B (p = 0.063). Comparing results between children with LTBI and those with TB disease differences were significant for IFN-γ ELISPOT only for AlaDH antigen (p = 0.021) and for IL-2 ELISPOT assay for AlaDH (p<0.0001) and TB 10.3 antigen (p = 0.043). ROC analyses demonstrated sensitivity of 100% and specificity of 81% of AlaDH-IL-2 ELISPOT assay in discriminating between latent and active TB using a cut off of 12.5 SCF per million PBMCs.
Our data suggest that IL-2 based ELISPOT with AlaDH antigen may be of help in discriminating children with active from those with latent TB.
Glomerular protein handling mechanisms have received much attention in studies of nephrotic syndrome. Histopathological findings in renal biopsies from severely proteinuric patients support the likelihood of protein endocytosis by podocytes. ClC-5 is involved in the endocytosis of albumin in the proximal tubule.
To investigate whether ClC-5 is expressed in the glomerular compartment and whether it has a role in proteinuric nephropathies. ClC-5 expression was studied using Real-time PCR in manually- and laser-microdissected biopsies from patients with type 2 diabetes (n 37) and IgA nephropathy (n 10); in biopsies of membranous glomerulopathy (MG) (n 14) immunohistochemistry for ClC-5 (with morphometric analysis) and for WT1 was done. Controls: cortical tissue (n 23) obtained from unaffected parts of tumor-related nephrectomy specimens.
ClC-5 was expressed at glomerular level in all biopsies. Glomerular ClC-5 levels were significantly higher in diabetic nephropaty and MG at both mRNA and protein level (p<0.002; p<0.01). ClC-5 and WT1 double-staining analysis in MG showed that ClC-5 was localized in the podocytes. ClC-5 ultrastructural immunolocalization was demonstrated in podocytes foot processes. Our study is the first to demonstrate that ClC-5 is expressed in human podocytes. The ClC-5 overexpression found in biopsies of proteinuric patients suggests that proteinuria may play a part in its expression and that podocytes are likely to have a key role in albumin handling in proteinuric states.