Biomedical Ti–Mo Alloys with Surface Machined and Modified by Laser Beam: Biomechanical,Histological, and Histometric Analysis in Rabbits

Purpose: In vivo bone response was assessed by removal torque, hystological and histometrical analysis on a recently developed biomedical Ti‐15Mo alloy, after surface modification by laser beam irradiation, installed in the tibia of rabbits. Materials and Methods: A total of 32 wide cylindrical Ti‐15Mo dental implants were obtained (10 mm × 3.75 mm). The implants were divided into two groups: 1) control samples (Machined surface – MS) and 2) implants with their surface modified by Laser beam‐irradiation (Test samples – LS). Six implants of each surface were used for removal torque test and 10 of each surface for histological and histometrical analysis. The implants were placed in the tibial metaphyses of rabbits. Results: Average removal torque was 51.5 Ncm to MS and >90 Ncm to LS. Bone‐to‐implant‐contact percentage was significantly higher for LS implants both in the cortical and marrow regions. Conclusions: The present study demonstrated that laser treated Ti‐15Mo alloys are promising materials for biomedical application.     

Skeletal Muscle Triacylglycerol Hydrolysis Does Not Influence Metabolic Complications of Obesity

Intramyocellular triacylglycerol (IMTG) accumulation is highly associated with insulin resistance and metabolic complications of obesity (lipotoxicity), whereas comparable IMTG accumulation in endurance-trained athletes is associated with insulin sensitivity (the athlete’s paradox). Despite these findings, it remains unclear whether changes in IMTG accumulation and metabolism per se influence muscle-specific and systemic metabolic homeostasis and insulin responsiveness. By mediating the rate-limiting step in triacylglycerol hydrolysis, adipose triglyceride lipase (ATGL) has been proposed to influence the storage/production of deleterious as well as essential lipid metabolites. However, the physiological relevance of ATGL-mediated triacylglycerol hydrolysis in skeletal muscle remains unknown. To determine the contribution of IMTG hydrolysis to tissue-specific and systemic metabolic phenotypes in the context of obesity, we generated mice with targeted deletion or transgenic overexpression of ATGL exclusively in skeletal muscle. Despite dramatic changes in IMTG content on both chow and high-fat diets, modulation of ATGL-mediated IMTG hydrolysis did not significantly influence systemic energy, lipid, or glucose homeostasis, nor did it influence insulin responsiveness or mitochondrial function. These data argue against a role for altered IMTG accumulation and lipolysis in muscle insulin resistance and metabolic complications of obesity.Obesity is a global public health problem and a major risk factor for insulin resistance and type 2 diabetes. These disorders are characterized by excess lipid accumulation in multiple tissues, primarily as triacylglycerols (TAGs). The lipotoxicity hypothesis suggests that this lipid excess promotes cellular dysfunction and cell death, which ultimately contribute to insulin resistance and metabolic disease (1). However, intracellular TAG accumulation is not always associated with adverse metabolic outcomes, suggesting that TAGs themselves are not pathogenic (2). In contrast, other non-TAG lipid metabolites such as fatty acids (FAs), diacylglycerols (DAGs), and ceramides have been shown to influence glucose homeostasis and insulin action by interfering with insulin signaling and glucose transport, promoting endoplasmic reticulum stress and mitochondrial dysfunction, and activating inflammatory and apoptotic pathways (reviewed in ref. 3). Nevertheless, the precise identities and sources of these bioactive lipid intermediates remain elusive (4,5). Furthermore, whether intracellular TAGs serve as a protective sink or a toxic source of deleterious lipid metabolites that contribute to insulin resistance remains unclear (6).Since skeletal muscle is the major contributor to insulin-mediated glucose disposal, lipid excess in this tissue could have serious implications for systemic glucose homeostasis and insulin responsiveness (7). Indeed, numerous studies have demonstrated a strong association between intramyocellular triacylglycerol (IMTG) accumulation and insulin resistance (reviewed in ref. 8). In contrast, endurance exercise training is characterized by IMTG accumulation and insulin sensitivity (the athlete’s paradox) (2). This variable association between IMTG accumulation and insulin responsiveness has largely been attributed to differences in the balance between lipid delivery and muscle oxidative capacity (8–10). Not surprisingly then, most studies have focused on the impact of muscle FA uptake and/or oxidation on glucose homeostasis and insulin action (11). However, experimental manipulations of these parameters cannot distinguish among the effects of IMTGs, IMTG metabolism, and other lipid intermediates. Furthermore, accumulating evidence suggests that muscle oxidative capacity cannot entirely explain differences in IMTGs or insulin responsiveness (12). These findings have led to speculation that dynamic IMTG metabolism (i.e., TAG synthesis or hydrolysis) may be critically involved in lipid-induced insulin resistance (6). However, few studies have specifically addressed the contribution of IMTG metabolism per se to this process.The regulated storage and release of IMTGs remain poorly understood, but require the coordinated action of synthetic enzymes (i.e., diacylglycerol acyltransferases [DGATs]), hydrolytic enzymes (i.e., adipose triglyceride lipase [ATGL] and hormone sensitive lipase [HSL]), and other lipid droplet proteins (6). Specifically, modulating IMTG synthesis in murine skeletal muscle alters IMTG content and systemic glucose homeostasis, supporting a role for IMTG metabolism in metabolic disease (13–15). However, the metabolic impact of modulating IMTG hydrolysis in vivo remains unclear. Global deletion of either ATGL (16–19) or HSL (20) has produced variable results. The former, but not the latter, results in massive IMTG accumulation with improvement in systemic glucose homeostasis, suggesting that inhibition of ATGL-mediated TAG hydrolysis protects against insulin resistance. In contrast, recent studies in cardiac muscle (21) and other tissues (22,23) indicate that ATGL-mediated TAG hydrolysis is required for mitochondrial function such that enhancing, rather than inhibiting, ATGL action may improve metabolic outcomes. Nevertheless, the autonomous role of skeletal muscle TAG catabolism in influencing muscle-specific and systemic metabolic phenotypes remains unknown.The goal of the current study was to understand the contribution of IMTG hydrolysis to tissue-specific and systemic metabolic phenotypes, particularly glucose homeostasis and insulin action, in the context of obesity. We therefore generated animal models with decreased (skeletal muscle-specific ATGL knockout [SMAKO] mice) and increased (muscle creatine kinase [Ckm]-ATGL transgenic [Tg] mice) ATGL action exclusively in skeletal muscle, and assessed the metabolic consequences at baseline and in response to chronic high-fat feeding. Interestingly, modulation of IMTG hydrolysis via ATGL action did not significantly influence glucose homeostasis, insulin action, or other metabolic phenotypes in the context of obesity despite dramatic changes in IMTG content.     

Cardiac iron removal and functional cardiac improvement by different iron chelation regimens in thalassemia major patients

Heart failure due to myocardial iron overload remains the leading cause of morbidity and mortality in adult thalassemia major (TM) patients. We evaluated the removal of cardiac iron and the changes of cardiac function by different iron chelation in TM patients by T2* cardiac magnetic resonance (CMR). Sixty-seven TM patients (27 males/40 females; mean age, 35 ± 6 years) on different chelation regimens underwent T2* CMR at baseline (t (0)), after 6-14 months (t (1)) and after 32 ± 7 months (t (2)). Patients were divided in four groups according to chelation treatment: group A (deferasirox), group B (deferoxamine), group C (combined treatment, deferoxamine plus deferiprone) and group D (deferiprone alone). Myocardial T2* at t (0) was <10 ms in 8 patients, between 10 and 20 ms in 22 patients and ≥ 20 ms in 37 patients. Progressive changes in T2* were observed at t (1) and t (2). Ten patients (10/36, 27.8 %) in group A, three patients (3/15, 20 %) in group B and three patients (3/12, 25 %) in group C moved from an abnormal T2* to normal values. We observed an improvement of left ventricular ejection fraction and a reduction of end-systolic and end-diastolic left ventricular volumes only in patients in group A with baseline cardiac T2* between 10 and 20 ms. Rigorous compliance to any chelation therapy at proper doses significantly improve myocardial T2*. Treatment with deferasirox significantly improves left ventricular function. Combination therapy seems to ameliorate cardiac T2* in a shorter period of time in severe siderosis.     

Neurogenesis in temporal lobe epilepsy: Relationship between histological findings and changes in dentate gyrus proliferative properties

Objective

The relationship between hippocampal histopathological abnormalities, epileptogenesis and neurogenesis remains rather unclear.

Methods

Tissue samples including the subgranular zone of dentate gyrus (DG) were freshly collected for tissue culture for neurospheres generation in 16 patients who underwent surgery for drug-resistant temporal lobe epilepsy. Remaining tissues were histologically examined to assess the presence of mesial temporal sclerosis (MTS) and focal cortical dysplasia.

Results

MTS was detected in 8 cases. Neurospheres were formed in 10/16 cases. Only three out of these 10 cases exhibited MTS; on the contrary 5/6 cases lacking neurosphere proliferation presented MTS. There was a significant correlation between presence of MTS and absence of proliferation (p = 0.0389). We also observed a correlation between history of febrile seizures (FS) and presence of MTS (p = 0.0004) and among the 6 cases lacking neurosphere proliferation, 4 cases (66.6%) had experienced prolonged FS. Among “proliferating” cases the percentage of granular cells pathology (GCP) was lower (20% vs 50%) compared to “non proliferating” cases.

Conclusion

A decreased potential to generate neurosphere from the SGZ is related to MTS and to alterations of dentate gyrus granule cells, especially in MTS type 1b and GCP type 1. These histological findings may have different prognostic implications, regarding seizure and neuropsychological outcome, compared to patients with other epileptogenic lesions (such as FCD, glioneuronal tumours, vascular lesions).     

Peri-implant collagen fibers around human cone Morse connection implants under polarized light: a report of three cases

Most of the histologic studies found in the literature on the peri-implant soft tissues have been done in animals and usually have been confined to mandibular implants fitted with healing or standard abutments. Few studies have investigated human peri-implant soft tissues. Moreover, the structure and dimensions of the peri-implant soft tissues in immediately loaded implants have not been investigated in depth. Human histologic data are valuable to validate animal models. This histologic and histomorphometric study evaluated the peri-implant soft tissues around three immediately loaded implants in humans. The implants were retrieved using a trephine and treated to obtain thin, ground sections. The sulcular epithelium was composed of approximately four to five layers of parakeratinized epithelial cells and had a length of approximately 1.2 to 1.3 mm. The junctional epithelium was composed of approximately three to four layers of epithelial cells and had a length of approximately 1.0 to 1.5 mm. Connective tissue attachment had a width of between 400 and 800 μm. Peri-implant collagen fibers, in the form of bundles (1- to 5-μm thick), began at the crestal bone and were oriented perpendicular to the abutment surface until 200 μm from the surface, where they became parallel running in several directions. Collagen fibers appeared to form a three-dimensional network around the abutment. No acute or chronic inflammatory cell infiltrate was present. Collagen fibers oriented in a perpendicular manner and in direct contact with the abutment surface were not observed in any of the specimens. This differentiated network of fibers may have clinical relevance as a mechanical protection of the underlying bone. These human histologic data are extremely valuable to validate and confirm those obtained from studies performed on animal models. Moreover, immediate loading of the implants did not compromise soft tissue integration.     

Histologic and histomorphometric evaluation of an implant retrieved 8 years after insertion in a sinus augmented with anorganic bovine bone and anorganic bovine matrix associated with a cell-binding peptide: a case report

Few histologic and histomorphometric reports are present in the literature regarding the peri-implant bone response around implants inserted in sinuses grafted with different biomaterials. Anorganic bovine bone (ABB) and anorganic bovine matrix with the addition of an active cell-binding peptide (PepGen P-15) are xenogenic materials that have been reported to present biocompatibility and osteoconductivity. A monolateral sinus augmentation procedure with ABB (50%) and PepGen P-15 (50%) was performed in a 54-year-old man. Two titanium implants with a sandblasted and acid-etched surface were inserted after 6 months. After an additional 6 months, a fixed prosthetic restoration was fabricated. One implant fractured in the coronal portion after an 8-year loading period and was removed using a 5-mm trephine bur. Few particles of both grafting materials were present in the peri-implant bone. No graft material particles were found in contact with the implant surface, and bone was always interposed between the graft materials and surface. No inflammatory cell infiltrate, multinucleated giant cells, or foreign body reaction cells were found. The tissues around the implant were composed of 51.4% ± 4.8% bone, 6.2% ± 0.7% ABB particles, 2.4% ± 0.5% PepGen P-15, and 40.0% ± 7.1% marrow spaces. The bone-implant contact percentage was 78.4% ± 4.1%. A sinus augmentation procedure using ABB and PepGen P-15 produced bone formation with subsequent implant osseointegration, which was still present after 8 years of implant loading.     

Episodic ataxia and severe infantile phenotype in spinocerebellar ataxia type 14: expansion of the phenotype and novel mutations

Journal of Neurology - Spinocerebellar ataxia type 14 (SCA14) is a dominantly inherited neurological disorder characterized by slowly progressive cerebellar ataxia. SCA14 is caused by mutations in...