The immunomodulation of enteric neuromuscular function: implications for motility and inflammatory disorders

Gastrointestinal motility and sensory perception are altered in a variety of mucosal inflammatory conditions of the gut, ranging from peptic esophagitis to ulcerative colitis. Studies in animal models now clearly indicate a causal relationship between the presence of mucosal inflammation and altered sensory-motor function. In many instances, these changes occur in the absence of any discernible encroachment of the deeper neuromuscular layers by the inflammatory infiltrate, which remains largely within the lamina propria. Accordingly, attention has focused on local sources of mediators, and recent studies indicate that smooth muscle cells and enteroglia are sources of and targets for cytokines such as interleukin 1 beta and interleukin 6. In several instances, neuromuscular dysfunction persists after mucosal inflammation has subsided; this state may be maintained by locally produced mediators. Studies also show the ability of enteric muscle to modulate lymphocyte function via major histocompatibility complex II-restricted antigen presentation. Clinical observation and experimental data also suggest that nerves modulate intestinal inflammation via local release of proinflammatory neuropeptides (substance P) and via the activation of extensive circuits that may involve the brain. Taken together, these findings provide plausible explanations for a variety of clinical scenarios ranging from inflammatory bowel disease to pseudo-obstruction syndromes and subgroups of functional bowel disorders.     

Prevalence and epidemiology of Schistosoma mansoni and S. haematobium infection in two areas of Egypt recently reclaimed from the desert

Projects are being carried out in many regions of Egypt to reclaim land from the desert for agriculture. This paper presents findings from a baseline epidemiologic study conducted in 1992 in two newly reclaimed areas near Ismailia, Egypt. In the first area, just east of the Suez Canal, 40.0% of the residents tested positive for Schistosoma mansoni and 1.7% tested positive for S. haematobium, while in the second area, 15 km southwest of Ismailia, 49.3% tested positive for S. mansoni and 3.3% tested positive for S. haematobium. The intensities of S. mansoni infection were moderately high, with a geometric mean egg count of 76 eggs/gram of feces among positive individuals in the first area, and 100 eggs/gram of feces in the second area. When compared with a previous study conducted in 1985, the prevalence of S. mansoni infection in the first area has increased from 21.7% to 42.1% among settlers in the last seven years, while that of S. haematobium has decreased from 7.8% to 1.7%. These trends may result from changes in irrigation practices or other alterations in the local environment. There is a risk of schistosomiasis becoming a major public health problem in reclaimed areas if adequate control measures are not taken.     

Evidence that luminant and equiluminant motion signals are integrated by directionally selective mechanisms

Three experiments tested whether motion information for nonequiluminant (luminant) and equiluminant dots affects direction judgments when both types of stimuli are moving simultaneously in the same display. The motion directions for the two sets of dots were manipulated to produce four direction differences (0 degrees, 30 degrees, 60 degrees, and 90 degrees). The equiluminant dots were moved in a perfectly correlated fashion, but the percentage of correlated motion for the luminant dots was varied. When subjects judged whether the directions of the equiluminant and luminant dots were the same or different, performance for the conditions with 0 degrees, 60 degrees, and 90 degrees difference improved as the percentage of correlated luminant motion increased. The same result occurred for a control display that contained two sets of luminant dots. However, for the 30 degrees difference, performance was at chance level for the control display, but dropped below chance for the equiluminant-luminant display. When subjects indicated just the direction of the luminant dots, judgments were not affected by equiluminant motion. Judgments for the equiluminant dots also were accurate, except for the conditions with 30 degrees difference; these responses were biased by the luminant motion, indicating some form of motion capture. The interactive effects are discussed in terms of a directionally selective mechanism that combines equiluminant and luminant motion signals.     

Aedes albopictus and Ae. triseriatus eggs survive waste tire processing

Tires that were either crudely chopped or more finely processed into shreds contained viable eggs. Field-collected remnants of 2-3 chopped tires contained viable Aedes albopictus eggs. After shredding tires seeded with mosquito eggs, 34 (4.6%) of an estimated 746 Ae. albopictus eggs and 21 (2.7%) of an estimated 774 Aedes triseriatus eggs survived. Chopped and shredded tire remnants may serve as a means of dispersing mosquitoes.     

Rapidly progressive herpetic retinal necrosis: a blinding disease characteristic of advanced AIDS

Eleven patients with rapidly progressive herpetic retinal necrosis (RPHRN) complicating AIDS were investigated retrospectively to study the disease spectrum, systemic involvement, and therapy. The mean CD4 cell count was 24/microL. There was a characteristic disease pattern with rapid progression, 82% bilaterality, relative resistance to intravenous antiviral therapy, and 70% retinal detachment. Varicella-zoster virus was the probable cause in 10 patients (detected by polymerase chain reaction in two eyes investigated), and herpes simplex virus was the probable cause in one. Cutaneous zoster occurred previously in 73% but was not concurrent. Seventy-three percent had central nervous system disease, possibly virus-related. RPHRN may be a local herpetic recrudescence in an immune-privileged site with transneural spread. Only four of 20 affected eyes retained useful vision. Poor ocular bioavailability, retinal ischemia, acquired drug resistance, and strain pathogenicity may underlie treatment failure. Acyclovir therapy appears relatively ineffective. Combined intravenous and intravitreal therapy with foscarnet and ganciclovir may be the best current management. Research advances are needed urgently.     

Observation of steady state in blood and urine following human ingestion of hexavalent chromium in drinking water

The uptake and elimination of Cr(VI) in a male volunteer who ingested 2 L/d of water containing 2 mg/L for 17 consecutive days was measured. Total chromium was measured in urine, plasma, and red blood cells (RBCs) for 4 d prior to and 2 wk after dosing (34 d total). The estimated bioavailability (2%) and the plasma elimination half-life (36 h) were consistent with our previous studies of Cr(VI) ingestion in humans. Steady-state chromium concentrations in urine and blood were achieved after 7 d of Cr(VI) ingestion. Both plasma and red blood cell (RBC) chromium concentrations returned rapidly to background levels within a few days after cessation of dosing. Since the concentration of chromium in the RBC should not decrease quickly if the chromium had entered the RBC as Cr(VI), these data support our prior work suggesting that concentrations of 10 mg Cr(VI)/L or less in drinking water of exposed humans appears to be completely reduced to Cr(III) prior to systemic distribution. Clinical chemistry data indicate that no toxicity occurred.     

Thalidomide: lack of mutagenic activity across phyla and genetic endpoints

The human and rabbit teratogen thalidomide has been tested for mutagenicity in a wide range of assays, ranging from bacterial gene mutation assays conducted in vitro to in vivo cytogenetic assays conducted using rabbits, and including a variety of human-derived tissues. Thalidomide was not mutagenic to 6 strains of Salmonella when tested both in the presence and absence of Aroclor-induced rat liver S9 mix. This inactivity was confirmed in strains TA98 and TA100 using a 1-h pre-incubation assay protocol with the same S9 mix (10% S9), and additionally, in strain TA98 using 3 concentrations of S9 (4%, 10% and 30% S9 in S9 mix). Thalidomide was not clastogenic either to cultured human lymphocytes (whole blood cultures, minus S9 mix) or to Chinese hamster ovary (CHO) cells treated in vitro. Further, no cytotoxicity was observed in purified human lymphocytes when exposed to thalidomide up to the limit of its solubility in the medium in the presence and absence of liver S9 from Aroclor-induced pregnant rabbit. The CHO assays were conducted without metabolic activation and in the presence of a variety of sources of auxiliary metabolic activation (PB/beta NP-induced rat liver S9 mix, pooled male and female human liver S9 mix, uninduced and Aroclor-induced pregnant rabbit liver S9 mix and foetal rabbit S9 mix). Thalidomide did not induce micronuclei in isolated human lymphocytes (minus S9 mix) and it was non-mutagenic to mouse lymphoma L5178Y TK+/- cells when tested to the limits of its solubility in the culture medium (+/- S9 mix). No indication of recombinogenic or clastogenic activity was observed for thalidomide when tested in Drosophila. In addition, it failed to induce chromosome aberrations in grasshopper neuroblasts when tested in the presence and absence of Aroclor-induced rat liver S9 mix. Some unusual chromosome morphologies were observed in the grasshopper cytogenetic preparations indicating a potential of thalidomide to interact with chromosomal proteins. However, this potential was not evident in the human lymphocyte micronucleus assay, and thalidomide was apparently not reactive to the proteins of the mouse skin, as it gave negative results in a mouse local lymph node assay for skin sensitizing agents. Thalidomide was inactive in bone marrow micronucleus assays conducted using males and females from two strains of mice, and female New Zealand white rabbits. It is concluded that thalidomide is neither a mutagen nor an aneugen. This conclusion is discussed within the context of the results of earlier mutagenicity studies, the recent claim that thalidomide may be a heritable germ cell mutagen to humans, and the current interest in thalidomide for the treatment of immune system-related diseases.