Botulinum toxin A for the treatment of achalasia

Pneumatic balloon dilatation of the esophagus is one of the current recommended treatment for achalasia. This procedure is associated with risks such as esophageal rupture. Surgery and percutaneous gastrostomy tube placement has been performed in severely affected individuals. The Botulinum Toxin A (BoTxA) is widely used to treat neuromuscular conditions in which spasticity is of concern. We present four cases in which BoTxA was used as an alternative of treatment and in which less invasive modalities were unsuccessful. The patients received a total of 80 units of BoTxA, applied to the submucosa in doses of 20 units in each predetermined quadrants to the lower esophageal sphincter. All patients demonstrated improvement of their symptoms without side effects in this study.     

Effect of mechanical deboning process on the fat stability of 3 tropical fish species stored at -10 degrees C

Maximum advantage of certain fish species captured with shrimp, at present not fully utilized, constitutes a necessity in Venezuela. The purpose of this research work was to evaluate the stability of three of those fish species: bagre, cunaro and caballa, based on the changes that might occur in their fat content. This was done by comparing both the edible part of the whole fish, as well as the deboned flesh of each of them. Evaluation of the changes was performed by means of the acid and peroxide indices, with previous fat extraction, and the thiobarbituric acid (TBA) index. On the other hand, the fatty acids profile of the three species studied was determined by gas chromatography. According to our findings, the greater alteration was detected in the deboned sample, obtaining the highest TBA and acidity index values of all species, on the third month of storage; then a reduction of these values was observed. On the other hand, the peroxide index presented heterogeneous values in the three species analyzed through their storage period. The predominant fatty acids were: palmitic (16:0) among the saturated, and oleic (18:1) among the unsaturated. A greater proportion of unsaturated fatty acids was found in the three species. An increment of these in the deboned sample with respect to the whole fish, was also observed.     

Osteogenesis imperfecta and coronary artery surgery. A case report

A new case of Osteogenesis Imperfecta (OI) suffering ischemic heart disease is reported. The patient was successfully operated on in our Institution and the bibliographic search showed only another case of such an association of diseases successfully treated by surgery. This patient proves that coronary artery surgery procedures are possible when OI complicates the cardiac ischemic syndrome.     

One-step purification of nisin A by immunoaffinity chromatography

The lantibiotic nisin A was purified to homogeneity by a single-step immunoaffinity chromatography method. An immunoadsorption matrix was developed by direct binding of anti-nisin A monoclonal antibodies to N-hydroxysuccinimide-activated Sepharose. The purification procedure was rapid and reproducible and rendered much higher final yields of nisin than any other described method.     

Angiotensin II mediates cell hypertrophy in vascular smooth muscle cultures from hypertensive Ren-2 transgenic rats by an amiloride- and furosemide-sensitive mechanism

Matrix metalloproteinases (MMP) are enzymes responsible for extracellular matrix degradation, a critical component influencing the growth and metastatic potential of cancer. The purpose of this study was to determine the in vitro effects of MMP inhibition on human pancreatic cancer cells and to document its effect on cancer growth in vivo. The effect of MMP inhibition was determined using the MMP inhibitor BB-94 and a moderately differentiated pancreatic cancer cell line (HPAC). In vitro, a dose response curve was generated over 5 days utilizing the MTT [3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. In vivo, using an established orthotopic model for pancreatic cancer (LD100 = 80 days), 22 nude mice with orthotopic tumors (30 were implanted) received either BB-94 or vehicle beginning 4 days prior to implantation and continuing to death or sacrifice on Day 70. Mice were weighted weekly. At death/sacrifice, tumors were weighted, volume determined, and metastases/ distant spread documented. In vitro, BB-94 had little effect on HPAC proliferation at 40 ng/ml but achieved progressively greater to near complete inhibition at doses up to 4000 ng/ml while maintaining cell viability. In vivo, BB-94 significantly increased length of survival (69 +/- 0.1 days vs. 56 +/- 3.1 days) and necropsy weight (25.7 +/- 1.67 g vs. 19.8 +/- 1.14 g) while decreasing metastatic rate (1 vs. 20) and tumor size (0.14 +/- 0.02 g vs. 0.65 +/- 0.1 g). MMP inhibition limits HPAC proliferation in a dose-dependent fashion without direct cytotoxic effects in vitro. Mice harboring orthotopic tumors treated with BB-94 demonstrated significant reductions in tumor weight, volume, and metastases which corresponded to increased animal weight and prolonged survival.     

Squamous cell carcinoma of the prostate. Presentation of a case and review of the literature

The authors report the case of a young patient with an aneurysm of the ascending aorta and moderate aortic incompetence, who underwent a conservative operation at our institution. Dilatation of the sinotubular junction, particularly at the level of the non-coronary sinus of the aortic valve with loss of coaptation between the corresponding leaflet and the two coronary leaflets, was identified at the time of surgery as major cause of valve insufficiency. During surgery, the dilated ascending aorta and pathologic aortic sinus were replaced with a 26 Hemashield prosthesis tailored according to the David guidelines. An intraoperative post-repair transesophageal echo exam showed that the aortic valve appeared to be working competently. The post-operative course was uneventful and at one year, an echographic check of the aortic valve showed that it was fully competent, with normal leaflet motion. Conservative surgery can be a good option in selected patients with ascending aortic aneurysm and aortic valve insufficiency.     

In vitro cytotoxicity of guanylhydrazones (MGBG and PGBG) on cultured Chinese hamster ovary cells

Periosteum was obtained within 10 days of injury from the site of 17 adult tibial diaphyseal fractures during internal fixation. Osteogenic cells, non-osteogenic cells and vascular elements were identified in situ using a variety of techniques. In all cases, the periosteum was thickened with randomly distributed plaques of cartilage and bone. Cells covering newly formed bone trabeculae expressed osteocalcin. Lectin-binding revealed high vascularity. Few mast cells were observed. Macrophages and acid phosphatase positive cells, some multinucleate, were observed in abundance. These findings suggest that the repair of the adult human diaphyseal fracture is similar to that of experimental fractures in rapidity of onset, high vascularity and in bone and cartilage formation. They differ in the fact that chondrogenesis and osteogenesis appear to be simultaneous in human fractures but sequential in experimental fractures. The paucity of mast cells suggests that they probably play no significant role in the repair of the human fractures.     

The proliferative response of HIV+ T-cells (CD4+ and CD8+) are severely suppressed via CD28 coactivation

Several studies have suggested that regulation of expression of the costimulatory molecule CD28 on the T-cell surface may play an important role in AIDS pathogenesis. In a study of T-cells from HIV+ donors, we find that activation with anti-CD3 plus anti-CD28 results in a mitogenic response which was approximately 86% suppressed for both CD4+ and CD8+ T-cells when compared to normal control cells. With PMA costimulation (instead of anti-CD28), the anti-CD3 response was suppressed much less, by 64 and 61%, respectively. With Con A as opposed to CD3 stimulation, the degree of suppression was less with either coactivator but still more severe with CD28 than with PMA coactivation. It has been reported that the CD28 subset of CD8+ T-cells is diminished in HIV+ individuals and could account for these results. It is possible as well that the CD28 costimulatory pathway in the CD4+ T-cells particularly is altered due to intervention by the HIV. While our data do not differentiate between these two possibilities, it show that the immune status is compromised in the HIV+ individual not only in terms of number of CD4+ T-cells, but in their activation response as well.     

Sakacin M, a bacteriocin-like substance from Lactobacillus sake 148.

The antagonistic activity of Lactobacillus sake 148 was evaluated during its growth on complex broth media and in a semisynthetic defined medium (SDM) with various supplements. The antagonistic activity was a growth-associated property, being detected and quantified when L. sake 148 was grown at either 4, 8, 16, 25 or 32 degrees C. The concentrated culture supernatant of L. sake 148 was subjected to purification by lyophilization and gel filtration. The purification procedure resulted in a small increase in its specific activity (7-fold) and in a low recovery of the original inhibitory activity (8%). Gel filtration analysis of the partially purified activity on Sephadex G-50 revealed an apparent molecular weight of 4640. The partially purified antagonistic activity of L. sake 148 was destroyed by treatment with proteolytic enzymes. However, the antagonistic activity was resistant to heat, having D-values at 121, 135 and 150 degrees C of 23.8, 17.4 and 15.2 min, respectively.