[Genome Editing Tools and their Application in Experimental Ophthalmology]. / Genome Editing Tools und ihr Einsatz in der experimentellen Augenheilkunde.

New genome editing tools in molecular biology are revolutionising precise genome surgery and have greatly influenced experimental ophthalmology too. Aside from the commonly used nuclease-based platforms, such as the zinc-finger nucleases (ZFN) and transcription activator-like effector nucleases (TALEN), CRISPR/Cas systems, clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) genes, perform very efficiently in site-specific DNA cleavage within living cells. DNA double strand breaks (DSB) are repaired through two different conserved repair pathways: NHEJ (non-homologous end joining) and HDR (homology directed repair). By using the correct DNA templates, these repair pathways can be used to knock out defective genes or to repair mutations. Genome editing technology lays the ground for new strategies in basic science, biotechnology, and biomedical science, as well as clinical studies with genome editing. Therapeutic gene editing strategies are now concentrating on diseases in the retina, due to the comparatively easy accessibility of the eye and with local application in vivo.

Reduced serum brain-derived neurotrophic factor in patients with first onset vitiligo.

PURPOSE: Vitiligo is an acquired pigmentary skin disease that can cause serious cosmetic problems. There have been numerous and well established studies that have demonstrated the comorbidity of various psychiatric disorders in patients with vitiligo. However, to our knowledge, there have been no studies investigating whether a psychiatric biomarker, such as brain-derived neurotrophic factor (BDNF), is associated with vitiligo. PATIENTS AND METHODS: This study was conducted in Namik Kemal University Medical Faculty, Departments of Dermatology and Psychiatry between January 2013 and September 2014. After meeting inclusion and exclusion criteria, serum BDNF levels were assayed in 57 patients with first onset vitiligo and no known current or past psychiatric disorder and compared with BDNF levels in 58 age and sex matched healthy subjects. RESULTS: The age and female/male ratios were similar between groups. The mean values of serum BDNF were 1.57±0.97 ng/dL and 2.37±1.73 ng/dL in the vitiligo group and in the healthy control group, respectively. The mean BDNF level was significantly higher in the healthy control group compared with the vitiligo group (t=2.76, P=0.007). CONCLUSION: This is the first study to compare serum BDNF levels between patients with vitiligo and healthy subjects. The reduced level of serum BDNF in patients with vitiligo may be directly related to the etiology of vitiligo or associated with the high percentage of psychiatric disorders in that patient population. Further studies are needed to support our preliminary results.

Distinct temperament and character profiles in first onset vitiligo but not in alopecia areata.

Alopecia areata (AA) and vitiligo (V) are diseases that are correlated with psychiatric disorders before, during and after diagnosis. The Temperament and Character Inventory (TCI) is a well-established approach for investigating personality traits in various psychosomatic diseases. The aim of this study is to compare and investigate the differences in the TCI between patients with first onset AA, patients with V and healthy controls (HC). Participants in the study included 42 patients with first onset AA, 50 adult patients with V and 60 HC who had no history or diagnoses of psychiatric or dermatological disorders. All participants were assessed with the TCI and the Dermatology Life Quality Index (DLQI). Among the temperament traits, the extravagance, disorderliness and total novelty-seeking scores were lower, and the worry and pessimism scores were higher in patients with V compared with patients with AA and the HC. The mean score of the enlightened second nature and the total self-directedness score of the character traits were higher in patients with V compared with patients with AA and the HC group. In the AA group, there was a negative correlation only between the reward dependence total score and the DLQI score. This study suggests that patients with first onset V have a distinct temperament, such as being unenthusiastic and unemotional, and character profiles, such as worry and pessimism, independent of their psychiatric comorbidities, and patients with AA do not have a different personality from the non-affected population.

Association of colon adenomas and skin tags: coincidence or coexistence?

OBJECTIVES: Skin tag (STs) are benign connective tissue tumors of the dermis. Some researchers have argued that there is a relationship between skin tag and colon polyps, although the physiopathological mechanisms underlying this relation were not well elucidated. In this study we aimed to investigate the co-existence of colonic adenomatous polyps and ST, additionally to shed light on the physiopathological mechanisms underlying this coincidence. PATIENTS AND METHODS: A total of 45 patients aged between 18 and 60 diagnosed with adenomatous colonic polyps and 45 sex, age, and socio-demographically matched subjects, had no polyps, were enrolled as the control group. Routine blood analysis of all participants, including serum glucose, total cholesterol, low-density lipoprotein cholesterol (LDL-C), (high-density lipoprotein cholesterol (HDL-C), triglyceride, insulin, IGF-1, and EGF, were performed. The chi-square and independent sample t or Mann Whitney U test were used to determine differences between groups. RESULTS: The number of participants with ST was significantly higher in the patient group (OR 7.067, p < 0.01). Serum levels of IGF-1 and EGF were statistically similar between the groups. In the subgroup analyses, no difference was found in serum levels of insulin, IGF-1, or EGF between patients with and without ST. However, higher serum levels of insulin and EGF were found in control subjects with ST (p < 0.01 and p < 0.01, respectively). For the entire study group, 67 participants had ST and 23 patients did not. Serum insulin, and IGF-1 were similar, while serum EGF levels were higher in patients with ST (p < 0.01). CONCLUSIONS: Findings of the present study may show a co-existence of colonic polyps and ST. Although previous studies have indicated that insulin resistance may play a role in the pathogenesis of both lesions in diabetic and obese patients, we found no indication of a relationship in nondiabetic and nonobese patients with increased levels of EGF in patients with ST, suggesting an alternative pathogenesis in this patient group.

The evaluation of analgesic effects of milnacipran and sertraline in tail-flick test.

INTRODUCTION: Antidepressant drugs are used in the treatment of pain as an adjuvant or alone. It has been shown that antidepressant drugs have analgesic effects in various diseases (diabetic neuropathy, low back pain, cancer pain etc.) Sertraline is a potent serotonin re-uptake inhibitor. Some antidepressant drugs inhibited both of the reuptake of serotonin and of noradrenaline. These drugs are called serotonin-noradrenaline re-uptake inhibitors (SNRIs). Milnacipran is a serotonin-noradrenaline re-uptake inhibitor. We have studied the analgesic effects of sertraline and milnacipran after acute and chronic application in tail-flick test in mice. METHODS: The analgesic effects of milnacipran (10, 30, 50 mg/kg) and sertraline (10, 20, 50 mg/kg) were measured after acute and chronic application in tail flick test. The analgesic effects of milnacipran (30 mg/kg) or sertraline (50 mg/kg) were evaluated after the application of L-NAME (10 mg/kg), naloxone (5 mg/kg), prazosin (1 mg/kg), ondansetron (0.1 mg/kg) in tail flick test. RESULTS: Milnacipran (30 mg/kg) and sertraline (50 mg/kg) produced statistically significant analgesic effect compared to their control values after acute and chronic application in tail-flick test. The analgesic effects of both milnacipran (30 mg/kg) and sertraline (50 mg/kg) in the presence of L-NAME (10 mg/kg), naloxone (5 mg/kg), ondansetron (0.1 mg/kg) and prazosin (1 mg/kg) were inhibited in tail-flick test. CONCLUSION: These results indicate that the analgesic effects of milnacipran and sertraline are related to nitrergic, opioidergic, serotonergic and adrenergic system (Fig. 8, Ref. 23).

mTOR phosphorylates IMP2 to promote IGF2 mRNA translation by internal ribosomal entry.

Variants in the IMP2 (insulin-like growth factor 2 [IGF2] mRNA-binding protein 2) gene are implicated in susceptibility to type 2 diabetes. We describe the ability of mammalian target of rapamycin (mTOR) to regulate the cap-independent translation of IGF2 mRNA through phosphorylation of IMP2, an oncofetal RNA-binding protein. IMP2 is doubly phosphorylated in a rapamycin-inhibitable, amino acid-dependent manner in cells and by mTOR in vitro. Double phosphorylation promotes IMP2 binding to the IGF2 leader 3 mRNA 5' untranslated region, and the translational initiation of this mRNA through eIF-4E- and 5' cap-independent internal ribosomal entry. Unexpectedly, the interaction of IMP2 with mTOR complex 1 occurs through mTOR itself rather than through raptor. Whereas depletion of mTOR strongly inhibits IMP2 phosphorylation in cells, comparable depletion of raptor has no effect; moreover, the ability of mTOR to phosphorylate IMP2 in vitro is unaffected by the elimination of raptor. Dual phosphorylation of IMP2 at the mTOR sites is evident in the mouse embryo, likely coupling nutrient sufficiency to IGF2 expression and fetal growth. Doubly phosphorylated IMP2 is also widely expressed in adult tissues, including islets of Langerhans.

Dynamically tuned coupled-resonator delay lines can be nearly dispersion free.

We investigate dispersion effects in dynamically tuned, coupled-resonator delay lines. Provided that the system is tuned to a zero-bandwidth state, a signal can be delayed indefinitely with almost no dispersion. We present a theoretical analysis of such a light-stopping system and verify the results using numerical simulations.

A case of rabbit syndrome treated with quetiapine.

Rabbit syndrome is characterized by rapid, fine, rhythmic movements of the perioral muscles along a vertical axis, mimicking the chewing actions of a rabbit. The present case demonstrates the possible usefulness of quetiapine as a mono-drug treatment strategy for dealing with rabbit syndrome and simultaneously treating psychotic symptoms.

The psychological impact of cutaneous leishmaniasis.

A psychiatric disorder would be associated with extensive, unsightly lesions on exposed body parts. Cutaneous leishmaniasis (CL) has long been endemic in Sanliurfa and is called 'beauty scar'. The aim of this study was to determine psychological impact of CL. Patients with active CL, with CL that had healed with scaring, and healthy controls were included in this case-control study. The Hospital Anxiety Depression Scale (HAD), Body Image Satisfaction Scale (BIS), and Dermatology Quality of Life Scale (DQL) assessments were performed to determine the psychological effect of CL. The patients with CL had significantly higher HAD anxiety and depression subscale scores than the control groups. Patients with CL have decreased body satisfaction and lower quality of life than those in the control group. It was found that CL patients with active lesions have the lowest quality of life score than other groups. CL lesions on exposed body parts such as the face and hands, active CL for more than 1 year, permanent scar formation, and social stigmatization cause anxiety, depressive symptoms, decreased body satisfaction and quality of life in CL patients.

Coupling of alkynylTMS derivatives with vinylic iodides. An efficient route to 1,3-enynes and dienes.

[reaction: see text] CuCl-promoted coupling of alkynylTMS derivatives with vinyl iodides leads to 1,3-enynes in high yield. Enynes prepared from homopropargylic alcohols undergo intramolecular hydrosilylation and subsequent silyl cleavage with TBAF to afford 1,3-dienes.

Lipase-mediated resolution of 4-TMS-3-butyn-2-ol and use of the mesylate derivatives as a precursor to a highly stereoselective chiral allenylindium reagent.

[reaction: see text]. An improved procedure for the resolution of 4-trimethylsilyl-3-butyn-2-ol has been developed. The mesylate derivatives of the resolved alcohols have been found to undergo highly enantio-, regio-, and diastereoselective additions to aldehydes, leading to homopropargylic alcohol adducts.

Synthesis of a C1-C21 subunit of the protein phosphatase inhibitor tautomycin: a formal total synthesis.

The synthesis of a C1-C21 subunit of tautomycin is described. The convergent route employs enantioenriched allenylstannane and zinc reagents derived from (S)-3-butyn-2-ol methanesulfonate. These reagents react with appropriate aldehyde segments to yield syn and anti adducts with high diastereoselectivity. The derived lithioalkynes are joined stepwise to a CO equivalent, (MeONMe)2C=O, to afford an intermediate ketone which is converted to the core spiroketal moiety of tautomycin upon acid treatment. Chain elongation by another addition of the aforementioned allenylzinc reagent to a spiroketal aldehyde proceeds with high diastereoselectivity to install the remaining stereocenters. The resulting homopropargylic alcohol adduct is converted to a methyl ketone through intramolecular hydrosilylation of the alkyne and Tamao oxidation of the derived five-membered siloxane. This ketone proved identical to an intermediate employed by Chamberlin in a prior total synthesis of tautomycin.

Frequency of dissociative disorders among psychiatric inpatients in a Turkish University Clinic.

OBJECTIVE: The aim of this study was to determine the rate of dissociative disorders among psychiatric inpatients in a university clinic in Turkey. METHOD: The Dissociative Experiences Scale was used to screen 166 consecutive inpatients admitted to the psychiatry clinic of a university hospital. The patients who had scores higher than 30 were matched for age and gender with 19 of the patients who scored below 10 on the scale. The patients in both groups were then interviewed with the Dissociative Disorders Interview Schedule by interviewers who were blind to their diagnoses and scores on the Dissociative Experiences Scale. Patients who were diagnosed as having a dissociative disorder according to the Dissociative Disorders Interview Schedule were then interviewed by a clinician. RESULTS: Twenty-four (14.5%) of the 166 patients had a score higher than 30 on the Dissociative Experiences Scale; 17 patients (10.2%) were diagnosed as having a dissociative disorder according to the Dissociative Disorders Interview Schedule. Nine patients (5.4%) had clinically confirmed dissociative identity disorder. CONCLUSIONS: A considerable proportion of the psychiatric inpatients in a Turkish university psychiatry clinic had dissociative disorder. Clinicians who work in general psychiatric inpatient units should be alert for chronic complex dissociative disorders.

Antibiotic iontophoresis in the management of burned ears.

Severe deformities of the ears are a distressing problem after burn injury. Successful management of chondritis has been elusive. Antibiotic iontophoresis has been used in the management of burned ears in patients who have been admitted to the St. Vincent Medical Center Burn Unit since 1983. There were 145 ear burns in 92 consecutive patients who received prophylactic penicillin or gentamicin iontophoresis and who were admitted from 1983 through 1990. A retrospective analysis of all patients who were admitted to the burn unit from 1967 to 1983 was done to review the outcome for patients with burned ears when conventional treatment was used. The incidence of infection, need for chondrectomy, and ear infection were virtually eliminated by management with antibiotic iontophoresis. In addition, no complications were noted when antibiotic iontophoresis was used. Antibiotic iontophoresis provides a safe, simple, and effective way to manage burned ears and thereby limits postburn ear deformities.

[Effect of a weak magnetic field on the course of an acute inflammation in the rat]. / Einfluss eines schwachen Magnetfeldes auf den Ablauf einer akuten Entzündung in der Ratte.

To determine the influence of weak magnetic field on the development of inflammations, a non-specific acute inflammation was induced in rats by subcutaneous injection of sterile SEPHADEX-gel in the lower dorsal quadrants. The magnetic field applied had a strength of 10 Gauss (equivalent to 20 times the magnetic field of the earth), rectangular curve and a frequency of 10 Hz. Following a field exposure of 2 and 3 days, cytological and biochemical analyses of the blood and inflammatory exudate were performed. Parameters were leucocytes and proteins in the blood and in the focus of inflammation as well as blood electrolytes. The protein values in the focus of inflammation of the control animals remained unchanged on the second and third day whereas in the animals exposed to the magnetic field, they increased from the second to the third day. In the blood similar effects could be seen, but they were not as pronounced. We conclude from these data that the magnetic field causes an increased exudation of serum proteins in the focus of inflammation. The cellular component remains unchanged.

[Electrolytic changes in the white mouse under the influence of weak magnetic fields]. / Elektrolytveränderungen in der weissen Maus unter dem Einfluss schwacher Magnetfelder.

On female white mice, the influence of weak magnetic fields on their electrolyte balance has been tested. Three types of magnetic fields, namely of a 50 HZ sinusoidal, a 50 Hz rectangular and a 10 Hz rectangular field have been applied, the latter mainly because of its similarity to some biologic rhythms and because some technical environments also tend to produce similar type of fields. The changes of electrolyte balance mentioned above were measured after one and seven days of exposure of the animals to those fields. The 50 Hz sinusoidal and 50 Hz rectangular type of the field shows - with the exception of Ca++ - no significant changes in the animals electrolyte balance, neither after one more after seven days. Ca++ levels however were in both cases significantly lower in test animals then in controls. A one days exposure to a 10 Hz rectangular field significantly lowers the Na+ and increases K+ levels. Almost reversed results are obtained after seven days, probably indicating overcompensation, after recovery. Since Na+ in liver homogenates after one days exposure is also low, we tend to hold the opinion that it must be excreted. Therefore it should be of some interest to check the balance of those hormones (e.g. angiotensin, vasopressin) which are closely connected with the above mentioned measured effects.