Capsaicin desensitization in vivo is inhibited by ruthenium red.

The effect of systemic administration of Ruthenium Red on the excitatory and desensitizing effect of capsaicin was investigated in rats. Ruthenium Red was injected s.c. 30 min before capsaicin was administered. The excitatory effect of capsaicin on corneal, perivascular and visceral afferents was not influenced by treatment with Ruthenium Red. However, determination of the neuropeptide content and evoked neuropeptide release in peripheral organs and dorsal spinal cord 48 h after treatment showed that Ruthenium Red attenuated the 'desensitizing' effect of capsaicin at peripheral, but not at central, endings of primary afferents. On the other hand, a capsaicin-elicited autonomic reflex mediated by visceral afferents was still obtained in 9 of 14 rats that had received Ruthenium Red and capsaicin. The results indicate that a single dose of Ruthenium Red, which does not reduce the acute excitatory effect of capsaicin, reduces the desensitizing effect of capsaicin on peripheral endings of primary afferents in vivo. This long-lasting protective effect of Ruthenium Red suggests that it is possible to pharmacologically differentiate between the acute and chronic effects of capsaicin.     

Sensory neuropeptides contribute to oedema formation in experimental burns

The role of primary sensory neuropeptides in experimental burns was investigated. It was shown that after scalding, substance P-like immunoreactivity is released into the lymphatic fluid of dogs. Substance P, injected intravenously, was shown to cause dose-dependent oedema formation in rat skin, as measured with the Evans blue-technique. Furthermore, capsaicin pretreatment, which depletes the neuropeptide content of primary sensory neurons, was shown to inhibit late oedema formation in rats.     

Wilson shaft osteotomy for hallux valgus

The results of a modified Wilson shaft osteotomy for hallux valgus in 77 feet of 51 patients were excellent or good in 62 feet after 2 to 4 years. The correction of the hallux valgus angle and intermetatarsal angle was excellent or good in 69 feet. The operation is technically simple provided dorsal angulation of the distal fragment is avoided in the early postoperative period.A     

Molecular characterization of Vibrio cholerae O1 strains isolated during cholera outbreaks in Guinea-Bissau.

In the present study, 19 strains of Vibrio cholerae O1 biotype El Tor isolated during outbreaks of cholera in Guinea-Bissau in 1987, 1994, and 1995 were characterized to investigate a possible epidemiological relationship among the isolates. On the basis of ribotyping with the restriction enzyme BglI, 5 strains isolated in 1987 showed two closely related ribotypes, while 14 strains isolated in 1994 and 1995 showed the same ribotype that was distinct from the ribotypes of strains isolated in 1987. Southern blot hybridization of BglI-digested genomic DNA with a cholera toxin probe demonstrated that the strains isolated in 1987 showed an identical cholera toxin genotype, whereas O1 strains isolated in 1994 and 1995 showed the same genotype that was distinct from the genotype of strains isolated in 1987. These results were supported by the results of antibiotic susceptibility testing, in which strains isolated in 1987 showed resistance to polymyxin B only, while each of the strains from 1994 and 1995 showed resistance to polymyxin B, trimethoprim-sulfamethoxazole, and the vibriostatic agent O/129. Although our results are based on a limited number of V. cholerae O1 strains, they suggest that the epidemic in Guinea-Bissau in 1994 and 1995 was due to the introduction of a new strain to the country.     

Gastrointestinal stromal tumors: an ultrastructural study

Gastrointestinal stromal tumors (GISTs) represent an enigmatic group of lesions of uncertain phenotype and biologic potential. Although earlier studies suggested smooth muscle cells, schwann cells, or neuronal differentiation, more recent evidence indicates that these tumors show phenotypic features that are similar to the interstitial cells of Cajal. Recently, investigators have begun to evaluate these lesions in a site-specific manner and have found that, in addition to morphologic differences between them, their biologic behavior also appears to be linked to their anatomic location. Many of these studies have emphasized the histologic and immunophenotypic features of GISTs in relation to their sites of origin, however, their site-specific ultrastructural characteristics have received little attention in the literature. In this study, we evaluated 34 GISTs (15 gastric, 12 small intestinal, 4 colonic, and 3 omental) for a variety of ultrastructural features in an effort to identify site-specific similarities and differences. Tumors predominantly composed of epithelioid cells were more commonly seen in gastric (60%) and omental (67%) tumors than in those of the small intestine (33%) and colon (0%). Cytoplasmic filaments and intercellular junctions were commonly seen in tumors from all locations, the filaments frequently forming paranuclear aggregates in the epithelioid cells. Tumors from all sites were composed of cells with surface filopodia and interdigitating cell processes, but in tumors of the stomach and omentum the filopodia were usually short and minimally intertwined, whereas those of small and large intestinal GISTs were characteristically long and complex. Basal lamina, though poorly formed, was present only in tumors of gastric and omental origin (13% and 67%, respectively). Pinocytotic vesicles were also seen in tumors from these sites (33% of gastric tumors and 67% of omental lesions) as well as those of the small intestine (17%) and the colon (25%). None of the gastric or omental tumors had microtubules; they were, however, seen in small intestinal (33%) and colonic (25%) stromal tumors. Skenoid fibers were seen in 33% of small intestinal GISTs and 1 metastatic gastric GIST. Overall, gastric and omental tumors have better developed features of myogenic differentiation and have blunt filopodia and minimally intertwined cell processes. Indeed, these 2 groups are indistinguishable ultrastructurally, raising the possibility that the genesis of omental GISTs is similar to that of gastric stromal tumors. Small intestinal stromal tumors have characteristic interdigitating cell processes and numerous elongate filopodia-like structures harboring intercellular junctions as well as microtubules and extracellular skenoid fibers. The constituent cells in colonic stromal tumors, while more reminiscent of small intestinal stromal, were frequently more primitive in appearance. In conclusion, GISTs from different anatomic locations share many overlapping ultrastructural characteristics; however, a few features are distinctive. It is hoped that these findings will aid in their recognition and contribute to the classification of this heterogeneous group of neoplasms.     

Peptide neuroanatomy of adjuvant-induced arthritic inflammation in rat

The influence of adjuvant-induced arthritis of the rat on central and peripheral peptide neuroanatomy was investigated by immunohistochemistry. The most striking feature of arthritic rats was the differential intensification of neuronal proenkephalin- and prodynorphin-related staining in dorsal horn. Changes were ipsilateral in monoarthritic and bilateral in polyarthritic rats as compared to controls. Opioid responsive neurons were target of substance P (SP) and calcitonin gene-related peptide (CGRP) fibers. Changes of SP and CGRP predominated in peripheral inflamed tissue and consisted of intensified immunostaining and an apparent sprouting of sensory fibers particularly around venules, in the epidermis and in areas infiltrated by immunocompetent cells. Opioid staining was absent from primary afferents but present in some immune cells of inflamed tissue. Endogenous antinociceptive opioids and pro-nociceptive/pro-inflammatory SP and CGRP may be crucial in the concerted response of the neuroimmune system to chronic inflammatory pain.     

The spectrum of aldolase B (ALDOB) mutations and the prevalence of hereditary fructose intolerance in Central Europe

We investigated the molecular basis of hereditary fructose intolerance (HFI) in 80 patients from 72 families by means of a PCR-based mutation screening strategy, consisting of heteroduplex analysis, restriction enzyme digest, DNA single strand electrophoresis, and direct sequencing. For a subset of patients mutation screening with DHPLC was established which turned out to be as fast and as sensitive as the more conventional methods. Fifteen different mutations of the aldolase B (ALDOB) gene were identified in HFI patients. As in smaller previous studies, p.A150P (65%), p.A175D (11%) and p.N335K (8%) were the most common mutated alleles, followed by c.360_363delCAAA, p.R60X, p.Y204X, and c.865delC. Eight novel mutations were identified in eight families with HFI: a small indel mutation (c.1044_1049delTTCTGGinsACACT), two small deletions (c.345_372del28; c.841_842delAC), two splice site mutations (c.113-1G>A, c.799+2T>A), one nonsense mutation (c.612T>G (p.Y204X)), and two missense mutations (c.532T>C (p.C178R), c.851T>C (p.L284P)). By mutation screening for the three most common ALDOB mutations by DHPLC in 2,000 randomly selected newborns we detected 21 heterozygotes. Based on these data and after correction for less common and private ALDOB mutations, HFI prevalence in central Europe is estimated to be 1:26,100 (95% confidence interval 1: 12,600-79,000).