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Aims/hypothesis Downregulation of levels of endothelial progenitor cells (EPCs) during in-vitro short-term exposure to high glucose concentrations relates to reduced activity of silent information regulator 1 (SIRT1) and increased synthesis of platelet-activating factor (PAF). We investigated the possible relationship between PAF and SIRT1 pathways in EPCs during altered glucose homeostasis. Methods SIRT1 and PAF receptor (PAF-R) levels were determined by western blot, RT-PCR and confocal laser-scanning microscopy. In-vivo experiments were performed on 48 type 2 diabetic patients (25 with poor glycaemic control and 23 with good glycaemic control) and 20 control individuals. In-vitro experiments with the PAF-R antagonist CV3988 were performed on EPCs isolated from leucocyte-rich buffy coat of healthy human donors. Results Decreased SIRT1 protein levels were observed in EPCs from type 2 diabetic patients compared with control individuals ( p  < 0.01). Notably, the SIRT1 level was consistently lower in patients with poor glycaemic control than in those with good glycaemic control ( p  < 0.01). Diabetic patients also showed an upregulation of PAF-Rs; this response occurred to a greater extent in individuals with poor glycaemic control than in those with good glycaemic control. In-vitro experiments confirmed that EPCs respond to PAF stimulation with decreased SIRT1 protein and SIRT1 mRNA levels. Moreover, reduction of SIRT1 levels and activity were abolished by CV3988. Conclusions/interpretation These findings unveil a link between PAF and SIRT1 pathways in EPCs that contributes to the deleterious effect of hyperglycaemia on the functional properties of EPCs, crucial in diabetes and peripheral vascular complications.

Dercum’s disease, or adiposis dolorosa, is a rare disorder which consists of multiple, painful lipomas within the subcutaneous tissue and has a distribution mainly in the abdomen and extremities. Dercum’s disease can be defined as in combination with chronic painful adipose tissue. Although the etiology of Dercum’s disease is not clear, it is thought to be a combination of a neurological and endocrine disorder. Treatment for this disease is centered at managing pain. Although there is no standard of care for managing pain, there are different pain management regimes that are promising.

Purpose. To report a case of a 34-year-old male with recurrent herpes zoster ophthalmicus (HZO) preceded by a 6-week cycle of anabolic steroids and high-dose amino acid supplementation. Case Presentation. A 34-year-old man presented to our institution for left eye pain for one week associated with a vesicular rash in the V1 dermatome, respecting the midline. The patient had no significant past medical or past ocular history, including systemic immunosuppressive agents or HIV. However, prior to the onset of his symptoms the patient had completed a 6-week course of anabolic steroids including trenbolone, deca-durabolin, and testosterone as well as high-dose arginine supplementation averaging more than 40 grams a day. The best-corrected vision was 20/25 OS with slit-lamp examination remarkable for punctate staining and pseudodendrites at 6 o’clock, outside the visual axis. The patient was treated with oral acyclovir 800 mg five times a day for seven days along with prednisolone QID and moxifloxacin QID which was tapered over a month. Four months after resolution, the patient developed a recurrent HZO keratitis preceded by another cycle of anabolic steroids and amino acid supplementation. Conclusion. In vitro L-arginine supplementation has been associated with the proliferation and virulence of a variety of herpes viruses. Anabolic steroids have also been demonstrated by various studies to negatively affect cell-mediated immunity necessary to prevent viral infection. Thus, it is possible that anabolic steroids in conjunction with increased L-arginine intake may have precipitated a recurrent HZO in a previously healthy, immunocompetent individual.

Background. Endometriosis usually occurs in the pelvis and often involves the ovaries, the uterosacral and broad ligaments, and the pelvic peritoneum. In rare instances, it can occur in the vasculature of the pelvis. Patients with endometriosis present with abnormal pain, menstrual cycle disruption and infertility. Management of endometriosis is usually surgical with excision of the tissue via laparoscopic means. Case. A 42-year-old Gravida 5, Para 2-0-3-2 patient with a 22 year history of endometriosis, who had had multiple laparoscopic endometriosis resections, total abdominal hysterectomy, and an exploratory laparotomy with bilateral salpingo-oophorectomy, presented with left pelvic pain when standing, dyspareunia, and a 3.7 cm cyst on ultrasound. The patient underwent laparoscopic vessel endometriosis resection and excision of endometriotic nodules from external iliac vessels. Final pathology report showed evidence of old endometriosis in all locations. On interval follow-up, the patient reported sustained relief from pain. Conclusion. Complete resection of endometriosis from large vessels can be successfully achieved laparoscopically by a well-experienced surgeon with delicate, proper techniques.

Background. Heterotopic pregnancy occurs when two pregnancies occur simultaneously in the uterus and an ectopic location. Treatment includes removal of the ectopic pregnancy with preservation of the intrauterine pregnancy. Treatment is done laparoscopically with either a Laparoendoscopic Single-Site Surgery (LESS) or a multiport laparoscopic surgery. Case. We present a case of a first trimester heterotopic pregnancy in a 42-year-old gravida 5, para 0-1-3-1 female with previous history of left salpingectomy, who underwent laparoscopic right salpingectomy and lysis of adhesions (LOA) via Single-Incision Laparoscopic Surgery (SILS). Conclusion. Although LESS for benign OB/GYN cases is feasible, safe, and equally effective compared to the conventional laparoscopic techniques, studies have suggested no clinically relevant advantages in the frequency of perioperative complications between LESS and conventional methods. No data on the cost effectiveness of LESS versus conventional methods are available. LESS utilizes only one surgical incision which may lead to decreased pain and better cosmetic outcome when compared to multiport procedure. One significant undesirable aspect of LESS is the crowding of the surgical area as only one incision is made. Therefore, all instruments go through one port, which can lead to obstruction of the surgeon’s vision and in some cases higher rate of procedure failure resulting in conversion to multiport procedure.

To the Editor: Le et al. (June 15 issue) 1 report that amphotericin B was superior to itraconazole in the treatment of talaromycosis and that the rates of adverse events were higher with amphotericin B use. However, some issues need to be discussed. The investigators did not report severity of illness or preexisting medical conditions. The treatment of talaromycosis depends on the severity of the infection, because itraconazole is recommended for milder forms of talaromycosis and amphotericin B or voriconazole for more severe forms. 2 The efficacy of treatment in both study groups can be misleading if, for instance, patients were not . . .

Pectin, one of the main components of the plant cell wall, is secreted in a highly methyl-esterified form and subsequently deesterified in muro by pectin methylesterases (PMEs). In many developmental processes, PMEs are regulated by either differential expression or posttranslational control by protein inhibitors (PMEIs). PMEIs are typically active against plant PMEs and ineffective against microbial enzymes. Here, we describe the three-dimensional structure of the complex between the most abundant PME isoform from tomato fruit (Lycopersicon esculentum) and PMEI from kiwi (Actinidia deliciosa) at 1.9-Å resolution. The enzyme folds into a right-handed parallel β-helical structure typical of pectic enzymes. The inhibitor is almost all helical, with four long α-helices aligned in an antiparallel manner in a classical up-and-down four-helical bundle. The two proteins form a stoichiometric 1:1 complex in which the inhibitor covers the shallow cleft of the enzyme where the putative active site is located. The four-helix bundle of the inhibitor packs roughly perpendicular to the main axis of the parallel β-helix of PME, and three helices of the bundle interact with the enzyme. The interaction interface displays a polar character, typical of nonobligate complexes formed by soluble proteins. The structure of the complex gives an insight into the specificity of the inhibitor toward plant PMEs and the mechanism of regulation of these enzymes.

We analyzed the 5' transcription control sequences of the human CD4 gene. We located the transcription initiation site and showed that the CD4 core promoter (positions -40 to +16) lacks a classical \"TATA\" or initiator positioning consensus sequence but directs precise and efficient transcription when coupled to the ubiquitously active simian virus 40 enhancer. The transcriptional activity of the CD4 gene promoter correlated with CD4 expression in various cell types. Interestingly, the CD4 core promoter also displayed a tissue-specific transcriptional activity. Within this fragment, three nucleic acid sequences are completely conserved in the murine CD4 gene. One of these sequences contains a perfect ETS consensus sequence. Another ETS consensus sequence is located 1060 nt upstream. Electrophoretic-mobility-shift assays showed that the core promoter ETS motif binds an Ets-related protein specifically expressed at high levels in CD4+cells. Moreover, in CD4-cells, overexpression of Ets-1 or Ets-2 efficiently and specifically activated transcription from the CD4 promoter and core promoter. These data indicate that Ets transcription factors play a central role in controlling CD4 gene expression, by binding to both a classical remote site and an unusual proximal activator sequence.

Itraconazole is a weakly basic drug, and dissolution of the drug is pH-dependent; thus the drug requires an acidic gastric environment for adequate absorption.1 Numerous studies have documented substantial variation in itraconazole exposure owing to the effect of food, interaction with coadministered drugs, and adherence.2 Guidelines recommend assessment of the exposure to itraconazole through therapeutic drug monitoring when the drug is used for treatment of systemic fungal diseases,3 including talaromycosis.4 Le et al. do not report on the exposure to itraconazole, but because capsules were used, underdosing of itraconazole might have been a factor in the lower response rate.

In this work the possibility of using hydrogels as body water retainers for a therapeutic aid in pathologies such as oedemas of various origins was explored. For such a purpose, the material requires a good compatibility and a controlled swelling capacity without altering the body electrolyte homeostasis. The hydrogel was designed to meet the swelling requirements with the physiological constraints and its biocompatibility was assessed either in vitro or in vivo. Absorption tests were performed in order to define the swelling behavior by varying the pH and ion content of the external solution. The hydrogel swelling capacity was assessed in the presence of various solvents, in order to evaluate its absorption capacity in solutions similar to biological fluids. In addition, the capacity of the gel to modify electrolyte homeostasis by adsorbing ions such as calcium, potassium and sodium was tested. In order to assess the gel biocompatibility after contact of the hydrogel with intestinal cells, arachidonic acid relase was determined. No significant intracellular increase of free arachidonic acid was found in the cells after up to 2 h of contact with the gel. The results suggest that, as far as brief periods are concerned, the gel does not cause an inflammatory response in intestinal cells.