2-Cl-MGV-1 Ameliorates Apoptosis in the Thalamus and Hippocampus and Cognitive Deficits After Cortical Infarct in Rats.

BACKGROUND AND PURPOSE: Focal cortical infarction causes neuronal apoptosis in the ipsilateral nonischemic thalamus and hippocampus, which is potentially associated with poststroke cognitive deficits. TSPO (translocator protein) is critical in regulating mitochondrial apoptosis pathways. We examined the effects of the novel TSPO ligand 2-(2-chlorophenyl) quinazolin-4-yl dimethylcarbamate (2-Cl-MGV-1) on poststroke cognitive deficits, neuronal mitochondrial apoptosis, and secondary damage in the ipsilateral thalamus and hippocampus after cortical infarction. METHODS: One hundred fourteen hypertensive rats underwent successful distal middle cerebral artery occlusion (n=76) or sham procedures (n=38). 2-Cl-MGV-1 or dimethyl sulfoxide as vehicle was administrated 2 hours after distal middle cerebral artery occlusion and then for 6 or 13 days (n=19 per group). Spatial learning and memory were tested using the Morris water maze. Secondary degeneration and mitochondrial apoptosis in the thalamus and hippocampus were assessed using Nissl staining, immunohistochemistry, terminal deoxynucleotidyl transferase dUTP nick end labeling, JC-1 staining, and immunoblotting 7 and 14 days after surgery. RESULTS: Infarct volumes did not significantly differ between the vehicle and 2-Cl-MGV-1 groups. There were more neurons and fewer glia in the ipsilateral thalamus and hippocampus in the vehicle groups than in the sham-operated group 7 and 14 days post-distal middle cerebral artery occlusion. 2-Cl-MGV-1 significantly ameliorated spatial cognitive impairment and decreased neuronal death and glial activation when compared with vehicle treatment (P<0.05). The collapse of mitochondrial transmembrane potential and cytoplasmic release of apoptosis-inducing factors and cytochrome c was prevented within the thalamus. Caspase cleavage and the numbers of terminal deoxynucleotidyl transferase dUTP nick end labeling+ or Nissl atrophic cells were reduced within the thalamus and hippocampus. This was accompanied by upregulation of B-cell lymphoma 2 and downregulation of Bax (P<0.05). CONCLUSIONS: 2-Cl-MGV-1 reduces neuronal apoptosis via mitochondrial-dependent pathways and attenuates secondary damage in the nonischemic thalamus and hippocampus, potentially contributing to ameliorated cognitive deficits after cortical infarction.

Experiences of healing therapy in patients with irritable bowel syndrome and inflammatory bowel disease.

BACKGROUND: The use and value of different complementary therapies requires investigation. In particular, qualitative research is required to understand the perceptions and experiences of patients who undergo healing therapy as one type of complementary therapy. The aim of this research is to consider patients perceptions and experiences following a course of healing therapy. METHODS: Twenty two patients took part in this study. This included 13 patients with irritable bowel disease (3 male, 10 female, 47.6 ± 15.0 years), 6 patients with ulcerative colitis (3 male, 3 female, 48.5 ± 25.6 years) and 3 female patients with Crohn's Disease (45.0 ± 5.2 years). Each patient undertook a single semi-structured interview following a course of healing therapy. The data was analysed using a thematic analysis. RESULTS: Three broad themes were identified from patient interviews (1) The understanding and expectation of healing (2) Experiences and reflection on healing (3) Impact and outcome of healing. The details of each theme are explored within the text, often revealing a unique experience of healing therapy. CONCLUSION: Patients were open towards the benefits that could be attained by healing, although most patients were not sure what healing would entail. Some patients expected to be relaxed by the sessions. However, the most consistent reports were that patients experienced a relaxing sensation that was generated within the session and lasted for a time period after the sessions. In addition to this the healing appeared to be associated with patients feeling more tolerant of their symptoms. Patients valued the therapist and their input into the healing process. It should be noted however, that this report cannot consider the efficacy of the treatment. Further details and experiences are considered within the article, including one negative experience.

Gut-directed hypnotherapy for irritable bowel syndrome: piloting a primary care-based randomised controlled trial.

BACKGROUND: In western populations irritable bowel syndrome (IBS) affects between 10% and 30% of the population and has a significant effect on quality of life. It generates a substantial workload in both primary and secondary care and has significant cost implications. Gut-directed hypnotherapy has been demonstrated to alleviate symptoms and improve quality of life but has not been assessed outside of secondary and tertiary referral centres. AIM: To assess the effectiveness of gut-directed hypnotherapy as a complementary therapy in the management of IBS. DESIGN OF STUDY: Randomised controlled trial. SETTING: Primary care patients aged 18-65 years inclusive, with a diagnosis of IBS of greater than 6 weeks' duration and having failed conventional management, located in South Staffordshire and North Birmingham, UK. METHOD: Intervention patients received five sessions of hypnotherapy in addition to their usual management. Control patients received usual management alone. Data regarding symptoms and quality of life were collected at baseline and again 3, 6, and 12 months post-randomisation. RESULTS: Both groups demonstrated a significant improvement in all symptom dimensions and quality of life over 12 months. At 3 months the intervention group had significantly greater improvements in pain, diarrhoea and overall symptom scores (P<0.05). No significant differences between groups in quality of life were identified. No differences were maintained over time. Intervention patients, however, were significantly less likely to require medication, and the majority described an improvement in their condition. CONCLUSIONS: Gut-directed hypnotherapy benefits patients via symptom reduction and reduced medication usage, although the lack of significant difference between groups beyond 3 months prohibits its general introduction without additional evidence. A large trial incorporating robust economic analysis is, therefore, urgently recommended.