Exploiting PI3K/mTOR signaling to accelerate epithelial wound healing

The molecular circuitries controlling the process of skin wound healing have gained new significant insights in recent years. This knowledge is built on landmark studies on skin embryogenesis, maturation, and differentiation. Furthermore, the identification, characterization, and elucidation of the biological roles of adult skin epithelial stem cells and their influence in tissue homeostasis have provided the foundation for the overall understanding of the process of skin wound healing and tissue repair. Among numerous signaling pathways associated with epithelial functions, the PI3K/Akt/mTOR signaling route has gained substantial attention with the generation of animal models capable of dissecting individual components of the pathway, thereby providing a novel insight into the molecular framework underlying skin homeostasis and tissue regeneration. In this review, we focus on recent findings regarding the mechanisms involved in wound healing associated with the upregulation of the activity of the PI3K/Akt/mTOR circuitry. This review highlights critical findings on the molecular mechanisms controlling the activation of mTOR, a downstream component of the PI3K–PTEN pathway, which is directly involved in epithelial migration and proliferation. We discuss how this emerging information can be exploited for the development of novel pharmacological intervention strategies to accelerate the healing of critical size wounds.     

Three-tesla MRI biphasic angiography: a method for preoperative assessment of the vascular supply in renal tumours—a surgical perspective

Purpose

The new generation of 3TMRI has improved spatial and time resolutions, which are favourable in imaging of the renal vasculature. In this study, we have compared the imaging findings of the renal blood vessels using 3TMRI and CT with intraoperative assessment of the renal vasculature as gold standard.

Methods

This prospective study was approved by the local ethical committee. Between 4/2011 and 12/2011, 80 patients with renal tumours underwent 3TMRA (angiography) (Magnetom SKYRA 3T, Siemens). Twenty of the patients were also examined with CT AG. The results of the CTA- and MRA-imaging studies were correlated with the intraoperative assessment of the renal vessels.

Results

Seventy patients (87.5 %) had a detailed intraoperative assessment of the renal vessels. The sensitivities for CTA and MRA were 88.2 and 88.6 %, respectively. All discrepancies between imaging studies and intraoperative findings were due to inability to identify small polar vessels. The results of MRA were concordant with CTA in 85.0 % of cases. The (three) discrepancies between MRI and CT were due to failure of MRI in identifying small polar vessels.

Conclusions

(1) 3TMRA gives detailed information about the renal vasculature including its topographical anatomy. (2) With MRI, small aberrant vessels are more frequently missed than with CTA. (3) CTA remains the gold standard. However, MRA may be used for planning of laparoscopic operations. (4) The quality of the 3D reconstruction is highly depending on the skills of the radiologist.     

Protective effects of Mentha piperita Linn on benzo[a]pyrene-induced lung carcinogenicity and mutagenicity in Swiss albino mice

The Editor-in-Chief has retracted the published paper "ProtectiveEffects of     

Clinical outcome with half-dose depot triptorelin is the same as reduced-dose daily buserelin in a long protocol of controlled ovarian stimulation for ICSI/embryo transfer: a randomized double-blind clinical trial (NCT00461916)

BACKGROUND: Traditional doses of depot GnRH agonist may be excessive for ovarian stimulation. We compared half-dose depot triptorelin (Group I) with reduced-dose daily buserelin (Group II) in a long protocol ICSI/embryo transfer through a double-blind randomized clinical trial. METHODS: Controlled ovarian stimulation (COS) was started by a pretreatment with oral contraceptives for 21 days. Then, 182 patients were randomized into two groups of 91. Group I received 1.87 mg triptorelin depot i.m. followed by daily s.c. injections of saline. Group II (reduced-dose protocol) received a bolus injection of i.m. saline followed by daily s.c. injections of 0.5 mg buserelin, which was then reduced to 0.25 mg at the start of human menopausal gonadotrophin stimulation. When transvaginal ultrasound showed at least two follicles of 16-20 mm diameter, HCG was given and ICSI was performed 40-42 h later. RESULTS: No significant differences were seen in the mean (SD) number of follicles at HCG administration, as our primary outcome [10.3 (4.4) in Group I versus 11.1 (4.2) in Group II, P = 0.180, mean difference = 0.86, 95% confidence interval 0.39-2.11]. The other early results of COS, clinical and ongoing pregnancy rates, or early pregnancy loss were also not significantly different between the groups. Group I endured longer stimulation period [11.2 (1.8) days versus 10.6 (1.9), P = 0.030]. CONCLUSIONS: Clinical outcomes were not significantly different between Group I and Group II.     

Grafted human chorionic stem cells restore motor function and preclude cerebellar neurodegeneration in rat model of cerebellar ataxia

Metabolic Brain Disease - Cerebellar ataxia (CA) is a form of ataxia that adversely affects the cerebellum. Cell replacement therapy (CRT) has been considered as a potential treatment for...     

Inhibition of histamine-induced pruritus by topical tricyclic antidepressants

Frequent antihistaminic side effects noted during treatment of depression by tricyclic drugs, as well as the high affinity of tricyclic antidepressants for H₁ receptors in mouse neuroblastoma cells, suggest possibly useful antihistaminic properties. We investigated the antipruritic activity of topically applied 5% solutions of doxepin hydrochloride (Adapin; Sinequan) and amitriptyline hydrochloride (Elavil) and compared such activity to that of a 5% solution of diphenhydramine and vehicle alone. Test solutions were applied to 25-cm² areas on the flexor forearms of forty subjects, and the development of itch to single drops of eight dilutions of histamine phosphate instilled in each area was reported over a 3-minute period. The lowest concentration of histamine able to elicit unequivocal itching in each treated area was the histamine itch threshold (HIT). Doxepin, amitriptyline, and diphenhydramine all produced significantly higher mean and median HITs (p < 0.01) than did vehicle control. Sixty-eight percent of subjects had a HIT ≥2 × 10^?4 mg/ml in doxepin-treated areas versus 58% for amitriptyline, 53% for diphenhydramine, and 25% for vehicle. Our data suggest that tricyclic antidepressants are effective topical antipruritic agents.