Differential regulation of MMP-2 in the gastrohepatic ligament of the gastroesophageal junction

Introduction

Ligamentous attachments maintain the normal anatomic position of the gastroesophageal (GE) junction. Failure of these elastic ligaments through an alteration in collagen synthesis, deposition, and metabolism may be a primary etiology of hiatal hernia formation. Differential expression of zinc-dependent matrix metalloproteinases (MMPs) is largely responsible for collagen remodeling. The purpose of this study was to survey baseline levels of MMPs in supporting ligaments of the GE junction from patients without hiatal hernia.

Methods

Following an institutional review board-approved protocol, plasma and tissue biopsies of the gastrohepatic ligament (GHL), gastrophrenic ligament (GPL), and phrenoesophageal ligament (PEL) were obtained in six patients without a hiatal hernia during laparoscopic anterior esophageal myotomy for achalasia. Total protein extracts from tissue biopsies were analyzed for elastases MMP-2, -9, and -12 and collagenases MMP-1, -3, -7, -8, and -13 using a multiplex profiling kit (R&D Systems, Minneapolis, MN). Data are reported as mean ± standard deviation. Statistical significance (p < 0.05) was determined using Tukey’s test and analysis of variance.

Results

In control patients without hiatal hernias, increased levels of MMP-2 (p < 0.02) were detected in the GHL compared with the GPL and PEL, respectively. Tissue levels of MMP-1, -12, and -13 were not detectable.

Conclusions

Gelatinase-A (MMP-2) is present in the GHL and plasma of control patients. The GHL may provide the primary GE junction supporting ligament to compare tissue from patients with type I (sliding) and type III (paraesophageal) hiatal hernias to examine the role of altered collagen metabolism in hiatal hernia formation.     

Microbial transformation of (-)-guaiol and antibacterial activity of its transformed products

Microbial transformation of the sesquiterpene (-)-guaiol (1) [1(5)-guaien-11-ol] was investigated using three fungi, Rhizopus stolonifer, Cunninghamella elegans, and Macrophomina phaseolina. Fungal transformation of 1 with Rhizopus stolonifer yielded a hydroxylated product, 1-guaiene-9 beta,11-diol (2). In turn, Cunninghamella elegans afforded two mono- and dihydroxylated products, 1-guaiene-3beta,11-diol (3) and 1(5)-guaiene-3beta,9 alpha,11-triol (4), while Macrophomina phaseolina produced two additional oxidative products, 1(5)-guaien-11-ol-6-one (5) and 1-guaien-11-ol-3-one (6). All metabolites were found to be new compounds as deduced on the basis of spectroscopic techniques. Compounds 1-6 were evaluated for their activity against several bacterial strains.     

Acute administration of clozapine and risperidone altered dopamine metabolism more in rat caudate than in nucleus accumbens: a dose-response relationship

The present study compares the extrapyramidal and neurochemical effects of clozapine and risperidone in rat caudate (corpus striatum) and nucleus accumbens (ventral striatum) dose-dependently. Animals injected with clozapine (2.5, 5.0 and 10.0 mg/kg IP) or risperidone (1.0, 2.5 and 5.0 mg/kg IP) in acute were sacrificed 1 h later to collect brain samples. Extrapyramidal side effects (EPS) in terms of locomotor activity and catalepsy were monitored in each animal after the drug or vehicle administration. Maximum cataleptic potentials were found only at high doses of clozapine (10.0 mg/kg; 60%) and risperidone (5.0 mg/kg; 100%). Neurochemical estimations were carried out by HPLC-EC. Both drugs at all doses significantly (p<0.01) increased the concentration of homovanillic acid (HVA), a metabolite of DA, in the caudate nucleus and decreased in nucleus accumbens. Levels of Dihydroxyphenylacetic acid (DOPAC) significantly (p<0.01) increased in the caudate by clozapine administration and decreased in the nucleus accumbens by the administration of both drugs in a dose-dependent manner. 5-Hydroxyindoleacetic acid (5-HIAA), the predominant metabolite of serotonin significantly decreased in the caudate and nucleus accumbens in a similar fashion. Levels of tryptophan (TRP) were remained insignificant in caudate and nucleus accumbens by the injections of two drugs. In caudate, clozapine and risperidone administrations significantly (p<0.01) decreased HVA/DA ratio and increased DOPAC/DA ratio in nucleus accumbens at all doses. The findings suggest the evidence for DA/5-HT receptor interaction as an important link in the lower incidence of EPS. The possible role of serotonin(1A) receptors in the pathophysiology of schizophrenia is also discussed.     

Pediatric caustic ingestion: 50 consecutive cases and a review of the literature

Caustic injury to the aerodigestive tract remains a significant medical and social concern despite various efforts to minimize hazards of caustic household products. Agents with a pH less than two or greater than 12 are extremely corrosive, causing damage that can range from mild to extensive, including esophageal perforation leading to mediastinitis and death at the extreme scale. Methods include retrospective case note review of all admissions to the otolaryngology unit with caustic injury that underwent esophagoscopy to the Children's Hospital Westmead between 1990 and 2007. A protocol‐based management system with antibiotics and steroids together with esophagoscopy at 48 hours was implemented. A total of 50 admissions were identified with an average follow‐up of 5 years. There were a total of 28 males and 22 females with a median age of 22 months. Forty‐nine cases (98%) were accidental. Thirty‐eight cases (76%) occurred within the interiors of the family home with the kitchen being the common location. Another seven (14%) occurred within the external environment of the home, usually in the garage or pool shed. The causative agents were varied with 37 (74%) being alkali, three cases (6%) being acidic, and other agents, such as chlorine bleach, being the remainder. The most frequently ingested alkalis were dishwashing powder and disinfectants closely followed by degreasers. Twenty‐five children (50%) drank directly from a container with the remainder ingesting granules or powder directly. At esophagoscopy, 17 cases (34%) had grade 1 injury and 10 (20%) had grade 2 injury. Fifty percent of patients of grade 2 injury subsequently developed strictures requiring multiple dilatations. Importantly, six cases (12%) had evidence of esophageal injury without oral injury. Caustic injuries continue to be a significant morbidity in the pediatric patient group. Most cases are still happening as a result of accidental ingestion from unmarked containers within reach of children at home. Oral injury is not always a useful marker of more significant distal injury. A protocol‐based management can identify children at risk for long‐term stricture earlier.