Effects of Hypericum extract on the acetylcholine release: a loose patch clamp approach.

The St. John's Wort (Hypericum perforatum) extract (Hp) represents one of the most useful natural therapeutic agents in the treatment of moderate and mild depression. The antidepressant effects of Hp are different, by a molecular mechanism point of view, when compared to those of other antidepressant drugs and, we think, a further pharmacological characterization is needed. It is suggested that the neurochemical effects of Hp could be bind either to its activity on the uptake of some mediators in the central nervous system or to the inhibition of some enzymatic activity at the receptor level. The present study carried out with the loose patch clamp (LPC) in the mouse neuromuscular junction, indicates a potentiation of the acetylcholine (ACh) action at the mouse neuromuscular junction. The spontaneous release of ACh was unaffected by Hp indicating that neither presynaptic nor postsynaptic function are modified by Hp. Indeed, both the frequency and the amplitude of the miniature end-plate currents (mepcs) were unmodified by Hp. Furthermore, the mepcs decay time (tau), i.e. the apparent cholinergic channel life time, was significantly increased after Hp treatment. The other parameter affected was the amplitude of the evoked end-plate currents (epcs) which was constantly and in a dose dependent manner increased by Hp. These findings suggest a possible action of Hp on the acetylcholinesterase (AChE) in terms of a reduction of the degradation rate of ACh.     

Pulmonary fibrolysis in a patient with idiopathic pulmonary fibrosis: improvement of clinical and radiological pattern after treatment with pirfenidone

Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, fibrosing interstitial pneumonia associated with the histologic and/or radiologic pattern of usual interstitial pneumonia (UIP). Nowadays, the high‐resolution computed tomography pattern of “definite UIP” is enough to define a diagnosis of UIP without histological proof. This is pivotal especially in elderly patients with comorbidities. Early recognition of IPF is relevant for its prognostic implication. Some pharmacological strategies have been proposing novel molecules that tend to slow lung function decline, even though without healing fibrosis. We report a case of ex‐heavy smoker male with IPF showing clinical and radiological improvement after 11 months of treatment with Pirfenidone. The definite diagnosis was challenging and it was reached by a multidisciplinary approach.     

Gastric endocrine tumors type I: treatment with long-acting somatostatin analogs

Gastric endocrine tumors associated with autoimmune chronic atrophic gastritis (gastric carcinoid type I) are almost exclusively benign lesions with little risk of deep invasion of the gastric parietal wall. For this reason, the role of octreotide in the treatment of these neoplastic lesions is controversial. Nine patients with more than five type I gastric endocrine tumors each <1 cm in size, without invasion of the muscularis propria and with Ki-67 index lower than 3%, were treated with long-acting somatostatin analogs for 12 months. After 6 months and again after 12 months, all the patients underwent upper gastrointestinal (GI) endoscopy with multiple biopsies. The plasma chromogranin A (CgA) levels and the gastrin levels in the serum were also determined. In all patients, the gastric neoplastic lesions disappeared after 12 months of somatostatin analog therapy. We also observed a significant reduction of CgA and gastrin levels at 6 and at 12 months of therapy as compared with the baseline values. We demonstrate that somatostatin analog treatment provokes the pathological regression of type I gastric carcinoids. This therapeutic approach should be considered as a valid option in selected patients with multiple type I gastric endocrine tumors.     

Bowel endometriosis: Colorectal surgeon’s perspective in a multidisciplinary surgical team

Endometriosis is a gynecological condition that presents as endometrial-like tissue outside the uterus and induces a chronic inflammatory reaction. Up to 15% of women in their reproductive period are affected by this condition. Deep endometriosis is defined as endometriosis located more than 5 mm beneath the peritoneal surface. This type of endometriosis is mostly found on the uterosacral ligaments, inside the rectovaginal septum or vagina, in the rectosigmoid area, ovarian fossa, pelvic peritoneum, ureters, and bladder, causing a distortion of the pelvic anatomy. The frequency of bowel endometriosis is unknown, but in cases of bowel infiltration, about 90% are localized on the sigmoid colon or the rectum. Colorectal involvement results in alterations of bowel habits such as constipation, diarrhea, tenesmus, dyschezia, and, rarely, rectal bleeding. Differential diagnosis must be made in case of irritable bowel syndrome, solitary rectal ulcer syndrome, and a rectal tumor. A precise diagnosis about the presence, location, and extent of endometriosis is necessary to plan surgical treatment. Multidisciplinary laparoscopic treatment has become the standard of care. Depending on the size of the lesion and site of involvement, full-thickness disc excision or bowel resection needs to be performed by an experienced colorectal surgeon. Long-term outcomes, following bowel resection for severe endometriosis, regarding pain and recurrence rate are good with a pregnancy rate of 50%.     

Patient-reported outcomes in subjects with neuroendocrine tumors of the pancreas

AIM: To assess the patient-reported outcomes (PROs) of pancreatic neuroendocrine tumor (PNET) patients. METHODS: Fifty-one consecutive patients (21 male,30 female, 61.0 ± 10.3 years) with proven PNETs were studied. An SF-12 questionnaire capable of exploring the physical (PCS) and mental (MCS) aspects of daily life was used. Four questionnaires were also used [12 items General Health Questionnaire (GHQ-12) for nonpsychotic psychiatric disorders, State Trait Anxiety Inventory (STAI) Y-1 and Y-2 for anxiety and BDI-Ⅱ for depressive symptoms] to explore the psychological aspects of the disease. Forty-four sex- and age-matched Italian normative subjects were included and evaluated using the SF-12, STAI Y-1 and Y-2 questionnaires.RESULTS: Seven patients refused to participate to the study; they were clinically similar to the 44 participants who agreed to complete the questionnaires. PNET patients had a PCS score (44.7 ± 11.0) were not significantly different from the norms (46.1 ± 9.9, P = 0.610), whereas the MCS score was significantly lower in patients (42.4 ± 13.0) as compared to the norms (48.2 ± 9.8, P = 0.036). GHQ-12 identified 11 patients (25.0%) as having non-psychotic psychiatric disorders. The STAI scores were similar in the patients and in the normative population. Finally, BDI-Ⅱ identified eight patients (18.2%) with moderate depression and 9 (20.5%) with mild depression whereas 27 patients (61.4%) had no depression. CONCLUSION: The PNET patients had a good physical but an impaired mental component of their quality of life; in addition, mild or moderate depressive symptoms are present in about 40% of PNET patients.     

Metformin in non-alcoholic steatohepatitis

There is no established treatment for steatohepatitis in patients who are not alcoholics. This disease is a potentially progressive liver disease associated with hepatic insulin resistance. Only a weight-reducing diet in overweight patients has proved effective. We treated 20 patients who had steatohepatitis but were not alcoholics with metformin (500 mg three times a day for 4 months), an agent that improves hepatic insulin sensitivity. When compared with the six individuals not complying with treatment, long-term metformin significantly reduced mean transaminase concentrations, which returned to normal in 50% of actively-treated patients. Also, insulin sensitivity improved significantly and liver volume decreased by 20%. Similar data have been reported in insulin-resistant ob/ob mice with fatty liver. A randomised-controlled study is needed.     

Biosensors for determination of total antioxidant capacity of phytotherapeutic integrators: comparison with other spectrophotometric, fluorimetric and voltammetric methods

Enzymatic electrodes based on superoxide dismutase (SOD) biosensors, working both in aqueous and non-aqueous solutions, recently developed by the present authors, were used to experimentally evaluate the antioxidant capacity of several phytotherapeutic diet integrators. The precision of this method of analysis was found to be reasonable (R. S. D. < or = 10%). The results were also compared with those obtained using a traditional spectrophotometric method as well as a spectrofluorimetric method described in literature. Lastly, the comparison was extended to another method based on cyclic voltammetry currently being trialled by the present authors.