Peripheral pain mechanisms

A promising new treatment for glioma involves Auger electron emitters such as 125I or 123I conjugated to deoxyuridine (IUdR). However, the presence in tumour deposits of non-proliferating cells with clonogenic potential poses a major limitation to this cycle-specific therapy. We have used multicellular tumour spheroids derived from the human glioma cell line UVW to study [125I]IUdR-targeted radiotherapy in aggregates containing cells in different proliferative states. Autoradiographic identification of labelled cells indicated that nuclear incorporation of [125I]IUdR decreased markedly with increasing size of spheroid. IUdR incorporation was maximal in the surface layer of cells and decreased with depth within spheroids. Radiopharmaceutical uptake corresponded closely to the regions of cell cycling as indicated by staining for the nuclear antigen Ki67. The uptake of drug was enhanced by increasing the duration of incubation from 52 h to 104 h. These observations suggest that significant sparing of non-cycling malignant cells would result from treatment delivered as a single injection of radiolabelled IUdR. To achieve maximal therapeutic effect. IUdR should be administered by multiple injections, by slow release from biodegradable implants or by slow-pump delivery.     

Transient liquid phase bonding of HfC-based ceramics

Transient liquid phase (TLP) bonding enables joining at lower temperatures than traditional bonding techniques and preserves the potential for high-temperature applications, making it particularly attractive for joining ultra-high-temperature ceramics (UHTCs) such as carbides and borides. The feasibility of a TLP joint between “pure” carbides has been recently demonstrated. The present study examines the interactions that occur between undoped HfC or MoSi₂-doped HfC and a Ni/Nb/Ni multilayer interlayer during TLP bonding. Bonding is performed at 1400 °C for 30 min in a high-vacuum furnace. SEM–EDS characterization shows that the reaction layer formed at the interlayer/ceramic interface contains mixed carbides and depending upon the ceramic, Ni–Nb–Hf, or Ni–Nb–Hf–Si, or Ni–Nb–Si alloys. Nanoindentation tests traversing the reaction layer between the bulk ceramic and Nb foil midplane also show a clear transition zone across which the indentation modulus and hardness vary. Crack-free joints have been obtained with undoped HfC. The addition of 5 vol% MoSi₂ introduces small (<5 μm long) isolated cracks within the reaction layer, whereas with 15 vol% MoSi₂ added, cracking was pervasive within the reaction layer. When the reaction layer exceeds a critical thickness, as in the case of the bond obtained with HfC doped with 15 vol% MoSi₂, residual stresses become sufficiently large to cause extensive cracking and bond failure. The results suggest a need to characterize and balance the positive role of additives on sintering with the potentially deleterious role they may have on joining.     

Persistent organochlorine compounds in fetal and maternal tissues: evaluation of their potential influence on several indicators of fetal growth and health

Some organochlorine compounds, such as polychlorinated biphenyls (PCBs), have a tendency to bioaccumulate in humans and predators at the top of the food chain. We have recently confirmed the transplacental transfer of these compounds and the present study has been designed on the same material with the aim of investigating their potential health effects on newborns from 70 pregnant women, resident in a Northern Italy industrial town. Organochlorine compounds [namely, p,p′-dichlorodiphenyltrichloroethane (p,p′-DDT), p,p′-dichlorodiphenyldichloroethene (p,p′-DDE), hexachlorobenzene (HCB), and PCBs] have been analyzed both in cord and maternal serum, placenta, and maternal subcutaneous adipose tissue by GC-MSD. p,p′-DDT levels in the adipose tissue resulted significantly (p < 0.05) related to birth length. Mothers of neonates born by preterm programmed caesarean delivery showed significantly (p < 0.005 for both) higher serum p,p′-DDE serum concentrations and p,p′-DDT levels in the adipose tissue, as compared to mothers delivering at term.     

Pericytes of Stria Vascularis Are Targets of Cisplatin-Induced Ototoxicity: New Insights into the Molecular Mechanisms Involved in Blood-Labyrinth Barrier Breakdown

The stria vascularis (SV) contributes to cochlear homeostasis and consists of three layers, one of which contains the blood-labyrinthic barrier (BLB), with a large number of bovine cochlear pericytes (BCPs). Cisplatin is a chemotherapeutic drug that can damage the SV and cause hearing loss. In this study, cell viability, proliferation rate, cytotoxicity and reactive oxygen species production were evaluated. The protein content of phospho-extracellular signal-regulated kinases (ERK) 1/2, total ERK 1/2, phospho-cytosolic phospholipase A₂ (cPLA₂), total cPLA₂ and cyclooxygenase 2 (COX-2) and the release of prostaglandin E2 (PGE2) and vascular endothelial growth factor (VEGF) from BCPs were analyzed. Finally, the protective effect of platelet-derived growth factor (PDGF-BB) on BCPs treated with cisplatin was investigated. Cisplatin reduced viability and proliferation, activated ERK 1/2, cPLA₂ and COX-2 expression and increased PGE2 and VEGF release; these effects were reversed by Dexamethasone. The presence of PDGF-BB during the treatment with cisplatin significantly increased the proliferation rate. No studies on cell regeneration in ear tissue evaluated the effect of the PDGF/Dex combination. The aim of this study was to investigate the effects of cisplatin on cochlear pericytes and propose new otoprotective agents aimed at preventing the reduction of their vitality and thus maintaining the BLB structure.     

Distinct Tomato Cultivars Are Characterized by a Differential Pattern of Biochemical Responses to Drought Stress

Future climate scenarios suggest that crop plants will experience environmental changes capable of affecting their productivity. Among the most harmful environmental stresses is drought, defined as a total or partial lack of water availability. It is essential to study and understand both the damage caused by drought on crop plants and the mechanisms implemented to tolerate the stress. In this study, we focused on four cultivars of tomato, an economically important crop in the Mediterranean basin. We investigated the biochemical mechanisms of plant defense against drought by focusing on proteins specifically involved in this stress, such as osmotin, dehydrin, and aquaporin, and on proteins involved in the general stress response, such as HSP70 and cyclophilins. Since sugars are also known to act as osmoprotectants in plant cells, proteins involved in sugar metabolism (such as RuBisCO and sucrose synthase) were also analyzed. The results show crucial differences in biochemical behavior among the selected cultivars and highlight that the most tolerant tomato cultivars adopt quite specific biochemical strategies such as different accumulations of aquaporins and osmotins. The data set also suggests that RuBisCO isoforms and aquaporins can be used as markers of tolerance/susceptibility to drought stress and be used to select tomato cultivars within breeding programs.     

Inhibitors of Mitochondrial Human Carbonic Anhydrases VA and VB as a Therapeutic Strategy against Paclitaxel-Induced Neuropathic Pain in Mice

Neuropathy development is a major dose-limiting side effect of anticancer treatments that significantly reduces patient’s quality of life. The inadequate pharmacological approaches for neuropathic pain management warrant the identification of novel therapeutic targets. Mitochondrial dysfunctions that lead to reactive oxygen species (ROS) increase, cytosolic Ca²⁺ imbalance, and lactate acidosis are implicated in neuropathic pain pathogenesis. It has been observed that in these deregulations, a pivotal role is played by the mitochondrial carbonic anhydrases (CA) VA and VB isoforms. Hence, preclinical studies should be conducted to assess the efficacy of two novel selenides bearing benzenesulfonamide moieties, named 5b and 5d, and able to inhibit CA VA and VB against paclitaxel-induced neurotoxicity in mice. Acute treatment with 5b and 5d (30–100 mg/kg, per os – p.o.) determined a dose-dependent and long-lasting anti-hyperalgesic effect in the Cold plate test. Further, repeated daily treatment for 15 days with 100 mg/kg of both compounds (starting the first day of paclitaxel injection) significantly prevented neuropathic pain development without the onset of tolerance to the anti-hyperalgesic effect. In both experiments, acetazolamide (AAZ, 100 mg/kg, p.o.) used as the reference drug was partially active. Moreover, ex vivo analysis demonstrated the efficacy of 5b and 5d repeated treatments in reducing the maladaptive plasticity that occurs to glia cells in the lumbar portion of the spinal cord and in improving mitochondrial functions in the brain and spinal cord that were strongly impaired by paclitaxel-repeated treatment. In this regard, 5b and 5d ameliorated the metabolic activity, as observed by the increase in citrate synthase activity, and preserved an optimal mitochondrial membrane potential (ΔΨ) value, which appeared depolarized in brains from paclitaxel-treated animals. In conclusion, 5b and 5d have therapeutic and protective effects against paclitaxel-induced neuropathy without tolerance development. Moreover, 5b and 5d reduced glial cell activation and mitochondrial dysfunction in the central nervous system, being a promising candidate for the management of neuropathic pain and neurotoxicity evoked by chemotherapeutic drugs.     

Epigenetic and Genetic Factors Related to Curve Progression in Adolescent Idiopathic Scoliosis: A Systematic Scoping Review of the Current Literature

Adolescent idiopathic scoliosis (AIS) is a progressive deformity of the spine. Scoliotic curves progress until skeletal maturity leading, in rare cases, to a severe deformity. While the Cobb angle is a straightforward tool in initial curve magnitude measurement, assessing the risk of curve progression at the time of diagnosis may be more challenging. Epigenetic and genetic markers are potential prognostic tools to predict curve progression. The aim of this study is to review the available literature regarding the epigenetic and genetic factors associated with the risk of AIS curve progression. This review was carried out in accordance with Preferential Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The search was carried out in January 2022. Only peer-reviewed articles were considered for inclusion. Forty studies were included; fifteen genes were reported as having SNPs with significant association with progressive AIS, but none showed sufficient power to sustain clinical applications. In contrast, nine studies reporting epigenetic modifications showed promising results in terms of reliable markers. Prognostic testing for AIS has the potential to significantly modify disease management. Most recent evidence suggests epigenetics as a more promising field for the identification of factors associated with AIS progression, offering a rationale for further investigation in this field.     

Urinary cytology of transitional-cell carcinoma

The authors report on their experience about urinary cytology in 1991. They studied 100 patients with cytology and histology, carried by cystoscopy and cold-mapping biopsy, trying to have notice about cytological value and proficiency.     

Serum hepatitis G virus (HGV) RNA in multitransfused thalassemics from eastern Sicily

To evaluate the efficacy of continuous administration of 50% nitrous oxide in oxygen for reducing pain during flexible fiberoptic bronchoscopy 32 children aged 3-60 months were randomly assigned to an experimental or a control group. Indications for endoscopy included persistent atelectasis (6), wheezing (10) cystic fibrosis (2) pneumonia (11) persistent cough (3). All patients received Midazolam (0.3 mg/kg) atropine (20 mcg/kg) intra rectaly 20 minutes before the procedure. The flexible fiberoptic bronchoscope (Olympus BF3C4) was inserted transnasally through a face mask. Topical anesthesia with 1% lidocaine hydrochloride (3 mg/kg) was applied to the nose, larynx, trachea and bronchial tree over 15 minutes through the suction chanel of the bronchoscope. All patients were monitored with a pulse oximeter and a cardiac monitor. The experimental group (n = 16) received 50% nitrous oxide in oxygen prior (3 minutes) and during flexible fiberoptic bronchoscopy, the control group (n = 16) received only oxygen. We measured pain of the children by a behavioral observation scale (Children's Hospital of Eastern Ontario Pain Scale: CHEOPS) at each phase of topical anesthesia during bronchoscopy in the two groups. At the end of bronchoscopy physician's satisfaction was scored by a visual analogue scale (VAS 0-100) in which 0 corresponded to absence of satisfaction. Nitrous oxide was associated with lesser pain scores than those with oxygen. Physician significantly preferred these procedure compared with oxygen. No complication occurred during procedure. Combined with local anesthesia midazolam and atropin the administration of 50% nitrous oxide in oxygen seems a better choice for flexible fiberoptic bronchoscopy in children and should be used routinely.