In vivo electroporation enhances plasmid-based gene transfer of basic fibroblast growth factor for the treatment of ischemic limb

BACKGROUND: Angiogenic therapy for ischemic tissues using angiogenic growth factors has been reported on an experimental and a clinical level. Electroporation enhances the efficiency of plasmid-based gene transfer in a variety of tissues. The purpose of this study was to evaluate the angiogenic effects of plasmid-based gene transfer using basic fibroblast growth factor (bFGF) in combination with electroporation. MATERIALS AND METHODS: The transfection efficiency of in vivo electroporation in rabbit skeletal muscles was evaluated using pCAccluc+ encoding luciferase. To evaluate the angiogenic effects of bFGF gene in ischemic limb, we constructed a plasmid, pCAcchbFGFcs23, containing human bFGF cDNA fused with the secretory signal sequence of interleukin (IL)-2. Then, 500 microg of pCAcchbFGFcs23 or pCAZ3 (control plasmid) was injected into the ischemic thigh muscles in a rabbit model of hind limb ischemia with in vivo electroporation (bFGF-E(+) group and LacZ-E(+) group). Other sets of animals were injected with pCAcchbFGFcs23 (bFGF-E(-) group) or pCAZ3 (LacZ-E(-) group) without electroporation. Then 28 days later, calf blood pressure ratio, angiographic score, in vivo blood flow, and capillary density in the ischemic limb were measured. RESULTS: Gene transfer efficiency increased markedly with the increase in voltage up to 100 V. Regarding angiogenic responses, calf blood pressure ratio, in vivo blood flow, and capillary density only in the bFGF-E(+) group were significantly higher than those in LacZ-E(-) group. Angiographic scores in the bFGF-E(+) and bFGF-E(-) groups were significantly higher than that in the LacZ-E(-) group. CONCLUSION: These data suggest that in vivo electroporation enhances bFGF gene transfer for the treatment of ischemic limb muscles.     

Glucose intolerance caused by a defect in the entero-insular axis: a study in gastric inhibitory polypeptide receptor knockout mice

Mice with a targeted mutation of the gastric inhibitory polypeptide (GIP) receptor gene (GIPR) were generated to determine the role of GIP as a mediator of signals from the gut to pancreatic beta cells. GIPR-/- mice have higher blood glucose levels with impaired initial insulin response after oral glucose load. Although blood glucose levels after meal ingestion are not increased by high-fat diet in GIPR+/+ mice because of compensatory higher insulin secretion, they are significantly increased in GIPR-/- mice because of the lack of such enhancement. Accordingly, early insulin secretion mediated by GIP determines glucose tolerance after oral glucose load in vivo, and because GIP plays an important role in the compensatory enhancement of insulin secretion produced by a high insulin demand, a defect in this entero-insular axis may contribute to the pathogenesis of diabetes.     

Psychiatric Patients Showing Irregular β Activities in EEGs and Treatment with Antiepileptic Drugs: A Report of 15 Cases†

Abstract: Fifteen psychiatric cases are reported who were clinically diagnosed as schizophrenic, affective disorders, or neurotic, but resisted standard medication regimens, all showing irregular β activities on EEGs. The cases tended to display symptoms in common, such as dysphoria, emotional instability or frequent physical complaints. These characteristic symptoms share something mutually with the symptoms shown in some epileptic patients or psychiatric patients with epileptic EEG abnormalities without clinical seizures. Antiepileptic drugs seemed more specifically effective to the above symptoms. More than half of these cases showed improvement on EEG findings such as a decrease in irregular β activities and an increase in rhythmicity or regularity of α activities along with clinical improvement with the administration of adjunctive antiepileptic drugs. These results suggest that the adjunctive administration of antiepileptic drugs to patients with irregular β activities on EEGs is clinically useful and an EEG examination has much value in psychiatric practice to find the criteria of drug therapy.     

Radioimmunoassay of serum group I and group II pepsinogens in normal controls and patients with various disorders

A radioimmunoassay (RIA) for human group I pepsinogens (PgI) in serum was developed, using Pgl purified from gastric mucosa. The sensitivity (0.7 μg/1) and reproducibility of the assay were satisfactory for clinical use. In normal controls, total serum pepsinogen (T-Pg) level was 58.9 ± 31.7 μg/1 (mean ± SD) (Pgl, 43.6 ± 25.0 μg/1; Pgll, 15.3 ± 11.1 μg/1). Peptic ulcer cases had elevated T-Pg levels (gastric ulcer, gastroduodenal ulcer and duodenal ulcer, in increasing order of magnitude). T-Pg levels were not useful for diagnosis of peptic ulcer because of a large overlap with normal controls. T-Pg levels were low in patients with gastric polyp and in aged subjects. In these groups, the decrease of Pgl was more marked than that of PgII.     

The Adult Patient with Eisenmenger Syndrome: A Medical Update after Dana Point Part II: Medical Treatment - Study Results

Eisenmenger syndrome is the most severe form of pulmonary arterial hypertension and arises on the basis of congenital heart disease with a systemic-to-pulmonary shunt. Due to the chronic slow progressive hypoxemia with central cyanosis, adult patients with the Eisenmenger syndrome suffer from a complex and multisystemic disorder including coagulation disorders (bleeding complications and paradoxical embolisms), renal dysfunction, hypertrophic osteoarthropathy, heart failure, reduced quality of life and premature death.For a long time, therapy has been limited to symptomatic options or lung or combined heart-lung transplantation. As new selective pulmonary vasodilators have become available and proven to be beneficial in various forms of pulmonary arterial hypertension, this targeted medical treatment has been expected to show promising effects with a delay of deterioration also in Eisenmenger patients. Unfortunately, data in Eisenmenger patients suffer from small patient numbers and a lack of randomized controlled studies.To optimize the quality of life and the outcome, referral of Eisenmenger patients to spezialized centers is required. In such centers, specific interdisciplinary management strategies of physicians specialized on congenital heart diseases and PAH should be warranted. This medical update emphasizes the current diagnostic and therapeutic options for Eisenmenger patients with particularly focussing on the medical treatment and corresponding study results.     

Usefulness of prone-position computed tomography as preoperative simulation prior to thoracoscopic esophagectomy for thoracic esophageal cancer

Purpose

The study aimed to evaluate the usefulness of prone-position computed tomography (CT) for predicting relevant thoracic procedure outcomes in minimally invasive esophagectomy (MIE) for thoracic esophageal cancer.

Materials and methods

A total of 59 patients underwent esophagectomy between May 2019 and December 2020 in Tokai University Hospital. Preoperative CT imaging was conducted with the patient in both the supine and prone positions, and the magnitude of change in the intramediastinal space was calculated. In the 56 patients (94.9%) who had undergone MIE, the effects of such a difference on the surgical outcomes were analyzed.

Results

A significant correlation of the magnitude of change in VE (distance between ventral aspect of the vertebral body and the midpoint of the esophagus) with the surgical outcome was revealed in the 17 patients (30.4%) in whom the magnitude of change in VE was over the 75th percentile. That is, in this subgroup, the magnitude of change in VE showed a negative correlation with the thoracic operation time (rs?=???0.57, p?=?0.01) and blood loss during the thoracic procedure (rs?=???0.46, p?=?0.01). Multivariate analysis identified a magnitude of change in VE?≥?9 mm (OR?=?0.14, p?=?0.03) as an independent risk factor for postoperative pneumonia.

Conclusions

This study indicates that preoperative prone-position CT imaging is useful for predicting the level of ease or difficulty of securing an adequate operative field, surgical outcomes, and the risk of postoperative pneumonia in MIE.