The effects of tualang honey on female reproductive organs, tibia bone and hormonal profile in ovariectomised rats - animal model for menopause

<p>Abstract</p> <p>Background</p> <p>Honey is a highly nutritional natural product that has been widely used in folk medicine for a number of therapeutic purposes. We evaluated whether Malaysian Tualang honey (AgroMas, Malaysia) was effective in reducing menopausal syndrome in ovariectomised female rats; an animal model for menopause.</p> <p>Methods</p> <p>The rats were divided into two control groups and three test groups. The control groups were sham-operated (SH) and ovariectomised (OVX) rats. The SH and OVX control rats were fed on 0.5 ml of distill water. The rats in the test groups were fed with low dose 0.2 g/kg (THL), medium dose, 1.0 g/kg (THM) and high dose 2.0 g/kg (THH) of Tualang honey in 0.5 ml of distill water. The administration was given by oral gavage once daily for 2 weeks. The reproductive organs (uterus and vagina), tibia bone and aorta were taken for histopathological examination while serum for hormonal assays.</p> <p>Results</p> <p>Administration of Tualang honey for 2 weeks to ovariectomised rats significantly increased the weight of the uterus and the thickness of vaginal epithelium, restored the morphology of the tibia bones and reduced the body weight compared to rats in the ovariectomised group. The levels of estradiol and progesterone, in honey treated groups were markedly lower than that in the OVX group. At low doses (0.2 g/kg; THL group) of Tualang honey there was an increased in serum free testosterone levels compared to OVX group (P < 0.01). Progesterone concentrations was significantly decreased in the OVX group as compared to SHAM group (P < 0.05).</p> <p>Conclusions</p> <p>Tualang honey was shown to have beneficial effects on menopausal (ovariectomised) rats by preventing uterine atrophy, increased bone density and suppression of increased body weight. Honey could be an alternative to HRT.</p

Remodeling the Proteostasis Network to Rescue Glucocerebrosidase Variants by Inhibiting ER-Associated Degradation and Enhancing ER Folding

Gaucher’s disease (GD) is characterized by loss of lysosomal glucocerebrosidase (GC) activity. Mutations in the gene encoding GC destabilize the protein’s native folding leading to ER-associated degradation (ERAD) of the misfolded enzyme. Enhancing the cellular folding capacity by remodeling the proteostasis network promotes native folding and lysosomal activity of mutated GC variants. However, proteostasis modulators reported so far, including ERAD inhibitors, trigger cellular stress and lead to induction of apoptosis. We show herein that lacidipine, an L-type Ca2+ channel blocker that also inhibits ryanodine receptors on the ER membrane, enhances folding, trafficking and lysosomal activity of the most severely destabilized GC variant achieved via ERAD inhibition in fibroblasts derived from patients with GD. Interestingly, reprogramming the proteostasis network by combining modulation of Ca2+ homeostasis and ERAD inhibition remodels the unfolded protein response and dramatically lowers apoptosis induction typically associated with ERAD inhibition

European clinical guidelines for Tourette syndrome and other tic disorders. Part II: pharmacological treatment

To develop a European guideline on pharmacologic treatment of Tourette syndrome (TS) the available literature was thoroughly screened and extensively discussed by a working group of the European Society for the Study of Tourette syndrome (ESSTS). Although there are many more studies on pharmacotherapy of TS than on behavioral treatment options, only a limited number of studies meets rigorous quality criteria. Therefore, we have devised a two-stage approach. First, we present the highest level of evidence by reporting the findings of existing Cochrane reviews in this field. Subsequently, we provide the first comprehensive overview of all reports on pharmacological treatment options for TS through a MEDLINE, PubMed, and EMBASE search for all studies that document the effect of pharmacological treatment of TS and other tic disorders between 1970 and November 2010. We present a summary of the current consensus on pharmacological treatment options for TS in Europe to guide the clinician in daily practice. This summary is, however, rather a status quo of a clinically helpful but merely low evidence guideline, mainly driven by expert experience and opinion, since rigorous experimental studies are scarce

Tumour-infiltrating lymphocytes predict for outcome in HPV-positive oropharyngeal cancer

Background: Human papillomavirus (HPV)-positive oropharyngeal cancer (OPSCC) is associated with improved survival compared with HPV-negative disease. However, a minority of HPV-positive patients have poor prognosis. Currently, there is no generally accepted strategy for identifying these patients.Methods: We retrospectively analysed 270 consecutively treated OPSCC patients from three centres for effects of clinical, pathological, immunological, and molecular features on disease mortality. We used Cox regression to examine associations between factors and OPSCC death, and developed a prognostic model for 3-year mortality using logistic regression analysis.Results: Patients with HPV-positive tumours showed improved survival (hazard ratio (HR), 0.33 (0.21–0.53)). High levels of tumour-infiltrating lymphocytes (TILs) stratified HPV-positive patients into high-risk and low-risk groups (3-year survival; HPV-positive/TILhigh=96%, HPV-positive/TILlow=59%). Survival of HPV-positive/TILlow patients did not differ from HPV-negative patients (HR, 1.01; P=0.98). We developed a prognostic model for HPV-positive tumours using a ‘training’ cohort from one centre; the combination of TIL levels, heavy smoking, and T-stage were significant (AUROC=0·87). This model was validated on patients from the other centres (detection rate 67%; false-positive rate 5.6%; AUROC=0·82).Interpretation: Our data suggest that an immune response, reflected by TIL levels in the primary tumour, has an important role in the improved survival seen in most HPV-positive patients, and is relevant for the clinical evaluation of HPV-positive OPSCC