Telomere shortening may be associated with human keloids

<p>Abstract</p> <p>Background</p> <p>Keloids are benign skin tumors that are the effect of a dysregulated wound-healing process in genetically predisposed patients. They are inherited with an autosomal dominant mode with incomplete clinical penetrance and variable expression. Keloids are characterized by formation of excess scar tissue beyond the boundaries of the wound. The exact etiology is still unknown and there is currently no appropriate treatment for keloid disease.</p> <p>Methods</p> <p>We analyzed sample tissues were obtained from 20 patients with keloid skin lesions and normal skin was obtained from 20 healthy donors. The telomeres were measured by Terminal Restriction Fragment (TRF) analysis and Real-Time PCR assay. Quantitative Real-Time RT-PCR analysis of hTERT gene expression was performed and intracellular ROS generation was measured.</p> <p>Results</p> <p>In this study, we determined whether telomeric shortening and the expression of human telomerase reverse transcriptase (hTERT) occurs in keloid patients. Using Terminal Restriction Fragment (TRF) analysis and Real-Time PCR assay, we detected a significant telomere shortening of 30% in keloid specimens compared to normal skin. Using quantitative Real-Time RT-PCR, telomerase activity was found absent in the keloid tissues. Moreover, an increase in ROS generation was detected in fibroblasts cell cultures from keloid specimens as more time elapsed compared to fibroblasts from normal skin.</p> <p>Conclusion</p> <p>Telomere shortening has been reported in several metabolic and cardiovascular diseases. We found that telomere shortening can also be associated with human keloids. Chronic oxidative stress plays a major role in the pathophysiology of several chronic inflammatory diseases. Here we found increased ROS generation in fibroblasts from keloid fibroblasts cell cultures when compared to normal skin fibroblasts. Hence we conclude that oxidative stress might be an important modulator of telomere loss in keloid because of the absence of active telomerase that counteracts telomere shortening.</p

Assessing the experience of using synthetic cannabinoids by means of interpretative phenomenological analysis

BACKGROUND: New psychoactive substances (NPS) have been increasingly consumed by people who use drugs in recent years, which pose a new challenge for treatment services. One of the largest groups of NPS is synthetic cannabinoids (SCs), which are intended as a replacement to cannabis. While there is an increasing body of research on the motivation and the effects associated with SC use, little is known about the subjective interpretation of SC use by the people who use drugs themselves. The aim of this study was to examine the experiences and personal interpretations of SC use of users who were heavily dependent on SC and are in treatment. METHODS: A qualitative research method was applied in order to explore unknown and personal aspects of SC use. Semi-structured interviews were conducted with six participants who had problematic SC use and entered treatment. The research was conducted in Hungary in 2015. We analyzed data using interpretative phenomenological analysis (IPA). RESULTS: Participants perceived SCs to be unpredictable: their initial positive experiences quickly turned negative. They also reported that SCs took over their lives both interpersonally and intrapersonally: the drug took their old friends away, and while initially it gave them new ones, in the end it not only made them asocial but the drug became their only friend, it hijacked their personalities and made them addicted. CONCLUSIONS: Participants experienced rapid development of effects and they had difficulties interpreting or integrating these experiences. The rapid alteration of effects and experiences may explain the severe psychopathological symptoms, which may be important information for harm reduction and treatment services. Since, these experiences are mostly unknown and unpredictable for people who use SCs, a forum where they could share their experiences could have a harm reducing role. For a harm reduction point of view of SCs, which are underrepresented in literature, it is important to emphasize the impossibility of knowing the quantity, purity, or even the number of different SC compounds in a particular SC product. Our study findings suggest that despite the adverse effects, including a rapid turn of experiences to negative, rapid development of addiction and withdrawal symptoms of SCs, participants continued using the drug because this drug was mostly available and cheap. Therefore, a harm reduction approach would be to make available and legal certain drugs that have less adverse effects and could cause less serious dependence and withdrawal symptoms, with controlled production and distribution (similarly to cannabis legalization in the Netherlands)

Inhibition of G Protein-Activated Inwardly Rectifying K+ Channels by Different Classes of Antidepressants

Various antidepressants are commonly used for the treatment of depression and several other neuropsychiatric disorders. In addition to their primary effects on serotonergic or noradrenergic neurotransmitter systems, antidepressants have been shown to interact with several receptors and ion channels. However, the molecular mechanisms that underlie the effects of antidepressants have not yet been sufficiently clarified. G protein-activated inwardly rectifying K+ (GIRK, Kir3) channels play an important role in regulating neuronal excitability and heart rate, and GIRK channel modulation has been suggested to have therapeutic potential for several neuropsychiatric disorders and cardiac arrhythmias. In the present study, we investigated the effects of various classes of antidepressants on GIRK channels using the Xenopus oocyte expression assay. In oocytes injected with mRNA for GIRK1/GIRK2 or GIRK1/GIRK4 subunits, extracellular application of sertraline, duloxetine, and amoxapine effectively reduced GIRK currents, whereas nefazodone, venlafaxine, mianserin, and mirtazapine weakly inhibited GIRK currents even at toxic levels. The inhibitory effects were concentration-dependent, with various degrees of potency and effectiveness. Furthermore, the effects of sertraline were voltage-independent and time-independent during each voltage pulse, whereas the effects of duloxetine were voltage-dependent with weaker inhibition with negative membrane potentials and time-dependent with a gradual decrease in each voltage pulse. However, Kir2.1 channels were insensitive to all of the drugs. Moreover, the GIRK currents induced by ethanol were inhibited by sertraline but not by intracellularly applied sertraline. The present results suggest that GIRK channel inhibition may reveal a novel characteristic of the commonly used antidepressants, particularly sertraline, and contributes to some of the therapeutic effects and adverse effects

Parathyroidectomy and survival in a cohort of Italian dialysis patients: results of a multicenter, observational, prospective study

Background: Severe secondary hyperparathyroidism (SHPT)&nbsp;is associated with mortality in end stage kidney disease (ESKD). Parathyroidectomy (PTX) becomes necessary when medical therapy fails, thus highlighting the interest to compare biochemical and clinical outcomes of patients receiving either medical treatment or surgery. Methods: We aimed to compare overall survival and biochemical control of hemodialysis patients with severe hyperparathyroidism, treated by surgery or medical&nbsp;therapy&nbsp;followed-up for 36&nbsp;months.&nbsp;Inclusion criteria were age older than 18&nbsp;years, renal failure requiring dialysis treatment (hemodialysis or peritoneal dialysis) and ability to sign the consent form. A control group of&nbsp;418 patients treated in the same centers,&nbsp;who did not undergo parathyroidectomy was selected after matching&nbsp;for&nbsp;age, sex, and dialysis vintage. Results: From 82 Dialysis units in Italy, we prospectively collected data of 257 prevalent patients&nbsp;who underwent parathyroidectomy (age&nbsp;58.2 ± 12.8 years; M/F: 44%/56%, dialysis&nbsp;vintage: 15.5 ± 8.4 years) and of 418 control patients who did not undergo parathyroidectomy (age&nbsp;60.3 ± 14.4 years; M/F 44%/56%; dialysis vintage 11.2 ± 7.6 y). The survival rate was higher in the group&nbsp;that underwent&nbsp;parathyroidectomy (Kaplan–Meier log rank test = 0.002). Univariable analysis (HR 0.556, CI: 0.387–0.800, p = 0.002) and multivariable analysis (HR 0.671, CI:0.465–0.970, p = 0.034), identified parathyroidectomy as a&nbsp;protective factor of overall survival. The prevalence of patients at KDOQI targets for PTH was lower in patients&nbsp;who underwent parathyroidectomy&nbsp;compared to controls (PTX vs non-PTX: PTH &lt; 150&nbsp;pg/ml: 59% vs 21%, p = 0.001; PTH at target: 18% vs 37% p = 0.001; PTH &gt; 300&nbsp;pg/ml 23% vs 42% p = 0.001). The control group received more intensive medical treatment&nbsp;with higher prevalence of vitamin D (65% vs 41%, p = 0.0001), calcimimetics (34% vs 14%, p = 0.0001) and phosphate binders (77% vs 66%,&nbsp;p = 0.002). Conclusions: Our data suggest that parathyroidectomy is associated with survival rate&nbsp;at 36 months, independently of biochemical control. Lower exposure to high PTH levels could represent an advantage in the long term. Graphical abstract: [Figure not available: see fulltext.]

Total knee arthroplasty in a patient with hypofibrinogenemia

Patients with afibrinogenemia or hypofibrinogenemia present a unique challenge to the arthroplasty surgeon as fibrinogen is a key contributor to hemostasis. Patients with these disorders are known to have a higher risk for postsurgical bleeding complications. We present the case of a patient with hypofibrinogenemia who underwent an elective total knee arthroplasty. Our colleagues in hematology-oncology guided us initially to achieve and maintain appropriate fibrinogen levels in the early perioperative period. However, the patient developed an acute joint effusion and subsequent infection 4 weeks after her initial operation. Her fibrinogen levels were noted to have fallen below the target range by that time, and it was also revealed that the patient failed to follow-up with hematology-oncology to monitor her levels. Based on our review of the available literature, we recommend that patient's fibrinogen levels be closely monitored and maintained ideally >100 mg/dL not only in the initial perioperative window but perhaps for the first 4-6 weeks postoperatively as well

Lipodystrophy and serum lipid abnormalities in HIV-positive sub-Saharan population on ART

To evaluate whether racial factors may be involved in the development of ART-induced lipodystrophy and/or lipid serum abnormalities, we carried-out a case-control study on all 23 consecutive anti-HIV-positive sub-Saharan black African patients observed from September 20fc01 to December 2001 (‘Cases’) and 23 Caucasian ‘Controls’ pair-matched for sex, age (G5 years), number of CD4 cells (G100 cells), clinical stage of HIV infection, overall duration (G3 months) of anti-retroviral treatment and type and duration (G3 months) of the last antiretroviral regimen. The cases, as compared with the controls, less frequently showed lipodystrophy (4.4 vs. 65.2%, P!0.001) and hypertriglyceridemia (8.8 vs. 56.5%, P!0.005), whereas the prevalence of subjects with hypercholesterolemia was similar in the two groups (30 and 39.1%, respectively). Overall, the prevalence of patients lacking both lipodystrophy and serum lipid abnormalities was markedly higher for the cases than for the controls (69.5 vs. 13%, P!0.001). This study seems to indicate that anti-retroviral-induced lipodystrophy and hypertriglyceridemia may be associated to some racial factor

Impact of occult HBV infection in HIV patients naive for anti-retroviral therapy. Dig & Liver Dis.

Objective: To study the impact of occult hepatitis B virus (HBV) infection in 115 consecutive anti-HIV-positive, hepatitis B surface antigen-negative patients, naive for antiretroviral treatment. Methods: Of these 115, 86 patients were followed for at least 6 months (range 6–36) with serial determinations of HIV RNA and HBV DNA by polymerase chain reaction and other laboratory tests. Results: Of the 86 patients having a follow-up, plasma HBV DNA was detected in 17 (19.8%), 13 on admission and four during follow-up. HBV DNA was more frequently found in patients with isolated anti-hepatitis B core (HBc; 35.5% of 31 cases) than in those lacking anti-HBc and anti-hepatitis B surface (8.8% of 41, P &lt; 0.005), or showing both (21.4% of 14). Twenty-eight patients (32.5%) experienced a hepatic flare during the follow-up; this event was more frequent in the 17 HBV-DNA-positive patients than in the 69 negative (64.7% versus 24.6%, P &lt; 0.005). Of the 13 HBV-DNA-positive patients on admission, 11 receiving HAART containing lamivudine became HBV-DNA negative, but two of these again became positive and experienced a hepatic flare during treatment and two both during and after lamivudine treatment. A hepatic flare also occurred under lamivudine treatment in two of the four patients in whom HBV DNA became detectable during follow-up. The role of immune reconstitution inflammatory syndrome and HAART in inducing a hepatic flare was found to be marginal in 49 patients with no HBV or hepatitis C virus marker. Conclusion: The study suggests that HBV occult infection, relatively frequent in anti- HIV-positive patients, is associated with hepatic flares