Results of magnetic resonance and computerized tomography studies of augmentation plastic surgery of the anterior cruciate ligament using carbon fibers. II

19 patients out of those described in part I were examined by MRI and CT. We quote MRI as an excellent new mean of imaging without exposure to ionising radiation which renders sufficient information about the internal knee-structures without surgical invasion. The signal density for the neoligament as well intraarticular as in the "over the top"-position gives evidence for the ingrowth of mesenchymal structures. The MRI diagnosis was proved by histological examination in 2 cases. Very good correspondence between clinic examination and the CT-images could be found. On top of that the tibial drilling holes could be shown in an excellent way. The CT-scan is a fine instrument to judge the postoperative state of the anterior cruciate ligament. The density measurement inside and outside the bone gives evidence for mesenchymal growth inside the carbon fibre structure and the existence of a new natural ligament.     

Mapping of murine YACs containing the genesCea2 andCea4 after B1-PCR amplification and FISH-analysis

PCR with primers specific for the murine B1 consensus sequence allows amplification of DNA from murine sources. We have used B1-PCR for amplifying yeast artificial chromosome (YAC) DNA which can be used to localize single YACs by fluorescencein situ hybridization. The genes for the pregnancy-specific glycoproteins Cea2 and Cea4, both belonging to the large carcinoembryonic antigen gene family, were localized by chromosomalin situ suppression hybridization of three YAC clones to murine chromosome 7A2-A3. This was facilitated by the use of the mouse lymphoma cell line WMP/WMP which contains nine pairs of Robertsonian fusion chromosomes.     

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.     

A prospective multicenter evaluation of immediately functionalized tapered conical connection implants for single restorations in maxillary anterior and premolar sites: 3-year results

Objectives

This multicenter prospective clinical trial investigated immediately provisionalized, anodized, conical connection, tapered implants with platform shifting in maxillary anterior and premolar sites.

Materials and methods

Patients requiring single-tooth implant-supported restorations in maxillary anterior and premolar sites were enrolled. Implants were immediately provisionalized and evaluated at insertion, 6 months, and annually thereafter. Outcome measures were marginal bone level change (ΔMBL), cumulative survival rate (CSR), and success rate, soft-tissue parameters, and oral health impact profile (OHIP). ΔMBL and Pink Esthetic Score were analyzed using Wilcoxon signed-rank tests. CSR was calculated using life table analysis. Other soft-tissue parameters were analyzed using sign tests.

Results

Of 94 enrolled patients (99 implants), 84 (88 implants) attended the 3-year follow-up. After an initial bone loss between implant insertion and 6 months (− 0.92 ± 1.23 mm), bone levels stabilized from 6 months to 3 years (0.13 ± 0.94 mm) with no significant change. The 3-year CSR was 98.9%, and the cumulative success rate was 96.9%. Papilla index scores of 2 or 3 were observed at 88.6% of sites at the 3-year visit compared with 32.8% at implant insertion. Improvements were observed for all other outcomes, including bleeding on probing, esthetics, plaque, and OHIP.

Conclusions

This restorative protocol was associated with high primary stability, patient satisfaction, stable bone levels, and an overall improvement of the soft tissue outcomes over a 3-year period.

Clinical relevance

The presented treatment is a viable option for single-tooth restorations of maxillary anterior teeth and premolars with successful short- to mid-long-term clinical outcomes.

     

An immune-sympathetic neuron communication axis guides adipose tissue browning in cancer-associated cachexia

Cancer-associated cachexia (CAC) is a hypermetabolic syndrome characterized by unintended weight loss due to the atrophy of adipose tissue and skeletal muscle. A phenotypic switch from white to beige adipocytes, a phenomenon called browning, accelerates CAC by increasing the dissipation of energy as heat. Addressing the mechanisms of white adipose tissue (WAT) browning in CAC, we now show that cachexigenic tumors activate type 2 immunity in cachectic WAT, generating a neuroprotective environment that increases peripheral sympathetic activity. Increased sympathetic activation, in turn, results in increased neuronal catecholamine synthesis and secretion, β-adrenergic activation of adipocytes, and induction of WAT browning. Two genetic mouse models validated this progression of events. 1) Interleukin-4 receptor deficiency impeded the alternative activation of macrophages, reduced sympathetic activity, and restrained WAT browning, and 2) reduced catecholamine synthesis in peripheral dopamine β-hydroxylase (DBH)–deficient mice prevented cancer-induced WAT browning and adipose atrophy. Targeting the intraadipose macrophage-sympathetic neuron cross-talk represents a promising therapeutic approach to ameliorate cachexia in cancer patients.

Cancer-associated cachexia (CAC) is an energy balance disorder causing unintended loss of body weight due to depletion of white adipose tissue (WAT) and skeletal muscle. This multiorgan and multifactorial syndrome affects up to 80% of cancer patients and is responsible for more than 20% of cancer-associated deaths (1). CAC impedes the effectiveness of anticancer therapies and drastically lowers patients’ quality of life (2).A long list of tumor-borne, often proinflammatory factors, including interleukin-6 (IL-6) (3), parathyroid hormone–related protein (PTHrP) (4), leukemia inhibitory factor (LIF) (5), zinc α-glycoprotein (6), or growth differentiation factor-15 (GDF-15) (7), trigger CAC in mouse models. However, the signaling cascades and catabolic mechanisms that lead to adipose- and muscle tissue wasting remain insufficiently understood (8, 9). IL-6 and PTHrP are among the best studied of these “cachexokines.” Their presence or absence is decisive for the development of CAC in cancer patients and animal models (4, 10–13). Thus, treatment with neutralizing antibodies against IL-6, the IL-6 receptor, or PTHrP ameliorates CAC in various mouse models of CAC (3, 4, 14, 15).CAC-associated WAT atrophy results from a metabolic switch toward decreased lipid synthesis and excessive degradation of lipid stores via enhanced triglyceride degradation (lipolysis) (9, 16). Induced lipolysis is observed in both humans and mice with CAC (17, 18). The absence of metabolic lipases at least partially ameliorates cachexia in murine cancer models (19). The metabolic or catabolic fates of lipolytic products, namely fatty acids (FAs) and glycerol, have not been fully clarified. These may provide energy and/or biosynthetic substrates for cancer cells to promote tumor growth or can be reesterified in WAT, creating an adenosine-triphosphate (ATP)-consuming futile metabolic cycle. Both of these pathways would contribute to the eventual loss of WAT during CAC (20).Another important catabolic pathway in CAC involves the direct oxidation of FAs and glycerol in adipose tissue. This process is promoted by the conversion of white to beige adipocytes called “WAT browning.” During WAT browning, adipocytes adopt a multilocular lipid droplet morphology; express genes that are typical for brown adipocytes, such as uncoupling protein-1 (UCP-1); exhibit elevated substrate oxidation rates; and dissipate energy as heat (21). WAT browning occurs in carcinogen-induced cancer models and genetically engineered mouse models as well as syngeneic and xenogeneic transplant models of murine cancers (3, 4, 22) and depends on the presence of cachexokines. WAT browning also occurs in humans suffering CAC or severe burn trauma (3, 23–25), but the cellular and molecular mechanisms underlying catabolic WAT remodeling in CAC remain unclear.Here, we demonstrate that a macrophage-sympathetic neuron signaling axis generates a high β-adrenergic tone resulting in beige adipogenesis, increased lipid degradation, and WAT atrophy in murine models of CAC. This mechanism triggering hypermetabolism in CAC may offer targets for prevention or treatment of the disease.     

Increased hepatic insulin sensitivity together with decreased hepatic triglyceride stores in hormone-sensitive lipase-deficient mice

Hormone-sensitive lipase (HSL) is a major enzyme for triglyceride (TG) lipolysis in adipose tissue. In HSL-knockout mice, plasma free fatty acid and TG levels are low, associated with low liver TG content. Because a decreased hepatic insulin sensitivity has been reported to be associated with high liver TG levels, our aim was to determine whether a hepatic TG content lower than normal, as observed in HSL-knockout mice, leads to increased hepatic insulin sensitivity. Therefore, hyperinsulinemic clamp experiments in combination with D-(3)H-glucose were used. Furthermore, hepatic insulin receptor and phosphorylated protein kinase B (PKB-P)/akt were analyzed by Western blotting. No significant differences where observed in insulin-mediated whole-body glucose uptake between HSL-knockout and control mice. Interestingly, hepatic insulin sensitivity of HSL-knockout mice was increased, because insulin caused a greater reduction in endogenous glucose production ( approximately 71% compared with approximately 31% in control mice; P < 0.05), despite decreased plasma adiponectin levels. PKB/akt phosphorylation and phosphatidylinositol-3-kinase activity was significantly higher in livers of HSL-knockout mice after insulin stimulation. In HSL-knockout mice, reduced hepatic TG stores result in an increased suppressive effect of insulin on hepatic glucose production, in line with an increased hepatic PKB-P/akt and phosphatidylinositol-3 kinase activity. Thus, hepatic insulin sensitivity is indeed increased after reducing hepatic TG stores below normal.     

Die Indikation zur postoperativen Infektprophylaxe nach Harnsteinoperationen

Zusammenfassung Bie 31 Patienten mit Harnsteinen wurde der Verlauf eines pr?- bzw. postoperativen Harninfektes untersucht. Auf Grund der Ergebnisse wird eine bakteriologische Untersuchung des Harnes 3 Wochen nach einer Harnsteinoperation empfohlen. Die chemotherapeutische bzw. antibiotische Prophylaxe ohne bakterielles Substrat ist nicht indiziert. Die Leukozytenz?hlung im Harn ist als Untersuchungsmethode bei Routinekontrollen von Harnsteinpatienten nicht geeignet.

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Summary 31 urinary stone formers, who underwent surgical treatment for their disease were investigated for the course of preoperative and postoperative urinary tract infection. According to the results of the study a bacteriological investigation of urine 3 weeks after operation is recommended. The postoperative use of prophylactic antimicrobials without underlying urinary tract infection is not advisable. Addis Count technique is not suited as a routine investigation technique in patients with urinary calculi.

     

Histologic and histomorphometric analysis of three types of dental implants following 18 months of occlusal loading: a preliminary study in baboons

The purpose of this study was to determine the percentage of 'bone area' (BA) and 'bone-to-implant contact' (BIC) of dental implants with different designs and surface modifications after functional loading. Three types of dental implants with fixed partial dentures were placed in the posterior jaws of adult baboons (commercially pure titanium (CpTi) screws, grit-blasted acid-etched (GBAE) screws, and titanium plasma-sprayed (TPS) cylinders), three of the same design per quadrant. After 18 months of functional loading, all implants investigated were successfully integrated in the jawbone and histologic and histomorphometric analyses were carried out. Statistical evaluation was performed with a mixed model with data given as least-square means and standard errors of the mean (SEM). Histologically, direct BIC without connective tissue interposed between implant surfaces and peri-implant bone was seen. Analysis of BA within 1 mm around implants showed significant differences between CpTi (50.5%) and TPS (39.7%) (+/-2.72 SEM; P<0.01) in the maxilla. To account for the different implant designs, absolute BIC was calculated. Significant differences were found between CpTi (23.9 mm) and TPS (15.1 mm) and between GBAE (27.2 mm) and TPS (15.1 mm) (+/-1.05 SEM; P<0.01) in the maxilla and between GBAE (26.5 mm) and TPS (19.6 mm) (+/-1.42 SEM; P<0.01) in the mandible. Overall, the data indicate that, in the maxilla, screw-shaped implants showed more absolute BIC than cylindrical implants, which had less maxillary than mandibular absolute BIC after 18 months of functional loading.