Spatial learning impairments in rats with selective immunolesion of the forebrain cholinergic system.

A monoclonal antibody to the low-affinity NGF receptor, 192 IgG, coupled to a cytotoxin, saporin, was recently introduced as an efficient selective neurotoxin for the NGFr-bearing cholinergic neurones in the rat basal forebrain. In the present study we report that an intracerebroventricular injection of this 192 IgG-saporin conjugate induces a severe, long-lasting spatial learning impairment, as assessed in the Morris water-maze task. This behavioural impairment was associated with 65-90% depletion of choline acetyltransferase activity (ChAT) in the hippocampus and cortex. ChAT activity associated with other cholinergic neurone systems in the brain (striatum, mesencephalon, spinal cord), was left virtually unaffected. This new immunotoxin holds great promise as a tool for selective and efficient lesions of the forebrain cholinergic system in functional and behavioural studies.     

Extensive training in a maze task reduces neurogenesis in the adult rat dentate gyrus probably as a result of stress

It has recently been shown that hippocampal neurogenesis can be modulated either directly or indirectly by ascending cholinergic inputs from the basal forebrain. In the present work, we sought to address whether extended training in a spatial navigation task would affect hippocampal neurogenesis in the presence of a severe and selective cholinergic depletion. Young female rats received stereotaxic injections of the immunotoxin 192 IgG-saporin into the basal forebrain nuclei and/or the cerebellar cortex. Starting from 4 to 5 weeks post-lesion, and for the subsequent 2 weeks, the animals were trained on paradigms of reference and working memory in the water maze and received single daily i.p. injections of bromodeoxyuridine (BrdU) at the end of each testing session. In line with previous observations, a dramatic 80% decrease in neuron proliferation was seen in the dentate gyrus of lesioned animals, as compared to vehicle-injected or intact controls. Interestingly, however, rats subjected to maze training over 2 weeks, irrespective of their learning success, exhibited significantly fewer newborn neurons than matched controls with no maze exposure. Thus, at least for the type of task used here, which has previously been shown to impose a certain degree of stress, extended training and learning does not appear to affect proliferation in the dentate gyrus.     

Polyomavirus BK DNA quantification assay to evaluate viral load in renal transplant recipients.

BACKGROUND: Several studies have disclosed a correlation between polyomavirus BK (BKV) and interstitial nephritis in renal transplant recipients and its quantification in urine and serum is therefore required to assess the role of BKV infection in nephropathy. OBJECTIVE: This paper describes a urine and serum BKV-DNA quantification protocol devised to evaluate the viral load. STUDY DESIGN: Screening of samples containing > or =10(3)/ml viral genome copies by a semi-quantitative polymerase chain reaction (PCR) assay is followed by precise quantification of the samples containing a high number of viral genomes in a quantitative-competitive (QC)-PCR assay. Generation of the competitor construct relied on the different sizes of wild-type and competitor amplicons. RESULTS AND CONCLUSIONS: Screening by semi-quantitative PCR selects samples with a high number of viral genomes for use in the more labor-intensive and -expensive QC-PCR assay and thus provides a handy means for quantitative DNA analysis of large numbers of samples. The results obtained in BKV-DNA quantification in urine and serum samples from 51 renal transplant recipients (22 on treatment with tacrolimus (FK506) and 29 on cyclosporine A (Cy A)) are interesting: BKV-DNA findings (43.1%) in urine samples are in agreement with the BKV urinary shedding reported in literature (5-45%). With regard to immunosuppressive treatment, the percentage of activation of the infection (revealed by BKV-DNA detection in urine samples) in the two groups of therapy is similar (40.9% vs 44.8%). The observation that the viral load in urine is dissociated with that of serum suggests that both parameters should be investigated in evaluation of the pathogenetic role of BKV reactivation in renal transplant recipients. Moreover, our BKV-DNA quantification protocol could be used to monitor viral load in urine and serum samples from renal transplant recipients so as to detect those at risk of nephropathy and monitor their response to immunosuppression reduction therapy if it occurs.     

Diet Quality Indices and Physical Activity Levels Associated with Adequacy of Gestational Weight Gain in Pregnant Women with Gestational Diabetes Mellitus

The aim of this study was to evaluate the Diet Quality Index (DQI) and the Physical Activity (PA) levels associated with adequacy of gestational weight gain in pregnant women with gestational diabetes mellitus (GDM). A total of 172 pregnant women with a single fetus and a diagnosis of GDM participated. Food intake was self-reported on the food frequency questionnaire and DQI was quantified using the index validated and revised for Brazil (DQI-R). To assess PA, the Pregnancy Physical Activity Questionnaire was administered. Gestational weight gain was classified, following the criteria of the Institute of Medicine, into adequate (AWG), insufficient (IWG), or excessive (EWG) weight gain. A multinomial logistic regression analysis was performed, with level of significance <0.05. The participants were divided into 3 groups: AWG (33.1%), IWG (27.3%), and EWG (39.5%). The analysis indicated that if the pregnant women PA fell into tertile 1 or 2, then they had a greater chance of having IWG, whereas those with the lowest scores on the DQI-R, whose PA fell into tertile 2, and pregestational obesity women had the greatest chance of having EWG. This study has shown that low PA levels may contribute towards IWG. On the other hand, a low final DQI-R score, representing inadequate food habits, low PA levels, and pregestational obesity may increase the chance of EWG in patients with GDM.     

Gain-of-Function Lrp5 Mutation Improves Bone Mass and Strength and Delays Hyperglycemia in a Mouse Model of Insulin-Deficient Diabetes

High fracture rate and high circulating levels of the Wnt inhibitor, sclerostin, have been reported in diabetic patients. We studied the effects of Wnt signaling activation on bone health in a mouse model of insulin-deficient diabetes. We introduced the sclerostin-resistant Lrp5^A214V mutation, associated with high bone mass, in mice carrying the Ins2^Akita mutation (Akita), which results in loss of beta cells, insulin deficiency, and diabetes in males. Akita mice accrue less trabecular bone mass with age relative to wild type (WT). Double heterozygous Lrp5^A214V/Akita mutants have high trabecular bone mass and cortical thickness relative to WT animals, as do Lrp5^A214V single mutants. Likewise, the Lrp5^A214V mutation prevents deterioration of biomechanical properties occurring in Akita mice. Notably, Lrp5^A214V/Akita mice develop fasting hyperglycemia and glucose intolerance with a delay relative to Akita mice (7 to 8 vs. 5 to 6 weeks, respectively), despite lack of insulin production in both groups by 6 weeks of age. Although insulin sensitivity is partially preserved in double heterozygous Lrp5^A214V/Akita relative to Akita mutants up to 30 weeks of age, insulin-dependent phosphorylated protein kinase B (pAKT) activation in vitro is not altered by the Lrp5^A214V mutation. Although white adipose tissue depots are equally reduced in both compound and Akita mice, the Lrp5^A214V mutation prevents brown adipose tissue whitening that occurs in Akita mice. Thus, hyperactivation of Lrp5-dependent signaling fully protects bone mass and strength in prolonged hyperglycemia and improves peripheral glucose metabolism in an insulin independent manner. Wnt signaling activation represents an ideal therapeutic approach for diabetic patients at high risk of fracture. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Transthoracic 2D echo color Doppler assessment of internal mammary artery to left anterior descending coronary artery graft

For noninvasive evaluation of anatomy and flow characteristics of internal mammary artery graft (IMA-graft), 2D echo-Color-Doppler (CDE) was performed in 60 patients (54 M, 6 F, mean age 54.1±6.9 y), who underwent coronary angiography 20.1 ±13 months after a coronary artery bypass graft (CABG).CDE was performed, using an echocardiographic unit equipped with a 5 MHz linear transducer.In all patients, measurements of IMA-graft diameter (mm), and peak systolic and diastolic flow velocity (cm/sec) were obtained at baseline and also in 16 patients after dipyridamole infusion (0.54 mg/Kg/min) and in 10 patients after sublingual nitroglycerin (NTG) (0.4 mg). Angiography showed the IMA-graft patency in 58/60 patients (96.8%).A typical biphasic flow was displayed by CDE in 49/58 patients (84.4%) with angiographic patency.Dipyridamole infusion increased both IMA-graft diameter and peak diastolic flow velocity (PDFV) from 2.28 ±0.51mm to 2.9 ±0.42mm and from 19.4 ±6.2 cm/sec to 93.9 ±29 cm/sec, respectively (p<0.0001).No significant modifications of peak systolic flow velocity (PSFV) were observed.NTG increased PDFV from 29.11 ±8 cm/sec to 41.88 ±7.20 cm/sec (p<0.005), while diameter and PSFV showed no statistically significant modifications.CDE is a useful diagnostic tool for noninvasive evaluation of IMA-graft patency both early after surgery and during long-term follow-up. CDE pharmacological stress improves the sensibility of the technique and it can provide indirect information about pathophysiology of recipient coronary vessel.     

Patient outcomes after therapeutic interchange of dolasetron for granisetron.

The impact of using therapeutic interchange (TI) of dolasetron for granisetron for the prevention of chemotherapy-induced nausea and vomiting (CINV) was evaluated. An outcomes evaluation was conducted in two cohorts of adult outpatients who had not previously received chemotherapy. Before the interchange, 20 patients were enrolled in a granisetron cohort, and after the interchange to dolasetron, 42 patients were matched to the initial cohort. Evaluations using the modified Functional Life Index--Emesis (MFLIE) compared changes in functional status before and after treatment. Nausea and vomiting frequency, satisfaction with antiemetics, reported adverse effects, changes in antiemetic therapy, and the use of antiemetics postchemotherapy were also evaluated. Success, defined as no vomiting and less than a 2.5-unit change in MFLIE score, was demonstrated in 45% of granisetron patients and 40% of dolasetron patients (p = 0.461). While functional status declined in both groups in response to chemotherapy, the changes in MFLIE scores did not differ between agents (-16.8 +/- 20.16 versus -19.39 +/- 26.36 in granisetron and dolasetron patients, respectively) (p = 0.650). Patients were equally satisfied with their prescribed antiemetic therapy, although less than half of patients achieved antiemetic success in the 72-hour study period. Self-reported adverse events attributed to serotonin type 3-receptor antagonist use were minimal and not significantly different between groups. The TI did not negatively affect patient outcomes and produced savings of $143,534 in the first year of the program. TI of dolasetron for granisetron for CINV did not affect functional status, nausea control, or patient satisfaction with antiemetic therapy.     

Titanium - castor oil based polyurethane composite foams for bone tissue engineering

Abstract

Polyurethanes (PU) foams with titanium particles (Ti) were prepared with castor oil (CO) and isophorone diisocyanate (IPDI) as polymeric matrix, and 1, 3 and 5?wt.% of Ti. Composites were physicochemically and mechanically characterized and their biocompatibility assessed using human dental pulp stem cells (HDPSC). PU synthesis was confirmed by FTIR, but the presence of Ti was detected by RAMAN, X-ray diffraction (peak at 2θ?=?40.2°) and by EDX-mapping. Materials showed three decomposition temperatures between 300?°C and 500?°C and their decomposition were not catalyzed by Ti particles. Compressive modulus (164–846?kPa), compressive strength (12.9–116.7?kPa) and density (128–240?kg/m³) tend to increase with Ti concentration but porosity was reduced (87% to 80%). Composites’ foams were fully degraded in acid and oxidative media while remained stable in distilled water. HDPSC viability on all composites was higher than 80% up to 14?days while proliferation dropped up to 60% at 21?days. Overall, these results suggest that these foams can be used as scaffolds for bone tissue regeneration.     

Selective release of cytokines,chemokines, and growth factors by minced skin in vitro supports the effectiveness of autologous minced micrografts technique for chronic ulcer repair

A new effective surgical procedure to repair chronic ulcers called minced micrografts technique has been recently reported. The technique consists in spreading a finely minced skin sample upon the wound bed. In this study, we investigate the in vitro release of cytokines (interleukin‐6, tumor necrosis factor‐α, interleukin‐1α, and granulocyte‐colony stimulating factor), chemokines (monocyte chemoattractant protein‐1 and growth‐related oncogene‐α), and growth factors (platelet‐derived growth factor, basic fibroblast growth factor, vascular endothelial growth factor, hepatocyte growth factor, and nerve growth factor) by minced (referred to as the minced sample) vs. not minced (referred to as the whole sample) human skin biopsy samples from the same donor. Factor release in the culture medium at different time points was detected using a multiplexed protein assay. The minced sample, which could behave like the skin fragments used in vivo in the autologous minced micrografts technique, expressed higher levels of tumor necrosis factor‐α, interleukin‐1α, platelet‐derived growth factor, and basic fibroblast growth factor, and lower levels of interleukin‐6, monocyte chemoattractant protein‐1, growth related oncogene‐α, and vascular endothelial growth factor compared with the whole sample. In conclusion, mincing of healthy skin may allow appropriate regulation of the inflammatory phase of wound healing and could induce overexpression of some growth factors, which facilitates the proliferative phase of healing.     

Diagnostic and prognostic value of magnetic resonance imaging in the detection of tumor depth of invasion and bone invasion in patients with oral cavity cancer

La radiologia medica - To evaluate the accuracy of preoperative contrast-enhanced magnetic resonance imaging (MRI) in the assessment of radiological depth of invasion (rDOI) and bone invasion in...