Lack of suppressive effects of mixtures containing low levels of methylmercury (MeHg), polychlorinated dibenzo-p-dioxins (PCDDS), polychlorinated dibenzofurans (PCDFS), and aroclor biphenyls (PCBS) on mixed lymphocyte reaction, phagocytic, and natural killer cell activities of rat leukocytes in vitro

Rat splenocyte mixed leukocyte reaction (MLR), splenic natural killer (NK) cell activity, and phagocytic activities of splenic, peritoneal, and peripheral blood leukocytes (PBLs) were evaluated in vitro to determine the immunotoxicity of mixtures containing low levels of methylmercury (MeHg), polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and Aroclor polychlorinated biphenyls (PCBs). The mixtures were based on the concentrations of the chemicals in fish flesh. Leukocytes from male Fischer rats were exposed to MeHg (0.1-2 microg/ml), PCDD/PCDF mixtures (1-15 pg/ml) of three PCDDs (2,3,7,8-tetrachlorodibenzo-p-dioxin, 1,2,3,7,8-pentachlorodibenzo-p-dioxin, and 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin) and two PCDFs (2,3,7,8-tetrachlorodibenzofuran and 1,2,3,7,8-pentachlorodibenzofuran), three Aroclor PCB (Aroclor 1242, 1254, and 1260) mixtures (0.01-0.5 microg/ml), or combinations of MeHg/PCB/PCDD/PCDF mixtures for 24 or 72 h before immunological assays. Phagocytosis and NK cell cytotoxicity were evaluated with a flow cytometer, and MLR of Fischer rat responder splenocytes cultured with mitomycin C-treated Long-Evans splenocytes by [3H]thymidine uptake. Exposure to MeHg (2 microg/ml) alone or with PCB/ PCDD/PCDF resulted in significant cytolethality in rat splenocytes, peritoneal leukocytes, and PBLs at 24 h exposure. Treatment with Aroclor PCB mixtures, PCDD/PCDF mixtures, 0.1 microg MeHg/ml (noncytolethal), or PCB/PCDD/PCDF mixtures with 0.1 microg MeHg/ml caused no suppression of splenocyte MLR response, splenic NK cell-mediated lysis of Yac-l cells, or phagocytosis of fluorescent beads by splenic, peritoneal, and peripheral blood phagocytic cells. The results indicate that in vitro exposure of rat leukocytes to low levels of MeHg, Aroclor PCB mixtures, PCDD/PCDF mixtures, or MeHg/PCB/PCDD/PCDF mixtures had no suppressive effects on the immune functions assayed, and thus produced no additive immunotoxicity. However, in order to predict the potential risk of these chemical mixtures to the human immune system, in vivo animal studies with blood (tissue) levels compatible with the levels of MeHg, PCBs, and PCDDs/PCDFs in exposed human populations should be evaluated.     

Keratitis complicated by endophthalmitis 3 years after astigmatic keratotomy

Endophthalmitis after keratotomy is rare and usually occurs soon after surgery. A 56-year-old woman with mild dry-eye symptoms developed keratitis complicated by endophthalmitis 3 years after astigmatic keratotomy (AK). The keratitis lasted for less than 1 day in the upper keratotomy incision. Corneal cultures yielded. Pseudomonas aeruginosa. Keratitis progressed to endophthalmitis 1 day after the detection of keratitis. The inflammation was controlled with intravitreal, subconjunctival, topical, and systemic antibiotics. This case demonstrates the potential risk of endophthalmitis developing very shortly after late keratitis of AK incisions. Vigorous early treatment and close follow-up seem justifiable in any keratitis associated with a keratotomy incision.     

Gastric emptying in rats with acetaminophen-induced hepatitis

The objective of this work was to study the gastric emptying (GE) of liquids in fasted and sucrose-fed rats with toxic hepatitis induced by acetaminophen. The GE of three test meals (saline, glucose and mayonnaise) was evaluated in Wistar rats. For each meal, the animals were divided into two groups (N = 24 each). Group I was fed a sucrose diet throughout the experiment (66 h) while group II was fasted. Forty-two hours after the start of the experiment, each group was divided into two subgroups (N = 12 each). Subgroup A received a placebo and subgroup B was given acetaminophen (1 g/kg). Twenty-four hours later, the GE of the three test meals was assessed and blood samples were collected to measure the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and acetaminophen. In group IB, the mean AST and ALT values were 515 and 263 IU/l, respectively, while for group IIB they were 4014 and 2472 IU/l, respectively. The mean serum acetaminophen levels were higher in group IIB (120 micrograms/ml) than in group IB (87 micrograms/ml). The gastric retention values were significantly higher in group IIB than in group IIA for all three test meals: saline, 51 vs 35%; glucose, 52 vs 38% and mayonnaise, 51 vs 29% (median values). The correlation between gastric retention and AST levels was significant (P < 0.05) for group IIB for the three test meals: r = 0.73, 0.67 and 0.68 for saline, glucose and mayonnaise, respectively. We conclude that GE is altered in rats with hepatic lesions induced by acetaminophen, and that these alterations may be related to the liver cell necrosis caused by the drug.     

Elevated inosine monophosphate levels in resting muscle of patients with stable chronic obstructive pulmonary disease

From January 1981 through October 1995, a total of 28 patients underwent surgery for metastatic lung tumors in our institute. A retrospective review and survival analysis of these patients are reported. There were 12 males and 16 females, with the mean age of 57 years. Of them, 20 patients had solitary lesions. Pulmonary metastasis was from the colon in 8 patients, from the breast in 5, from the stomach and the uterus in each 3, from the bladder, the rectum and the soft tissue in each 2, and from the kidney, the ovarium and the thyroid in each 1. A lobectomy was performed in 22 patients, 17 of whom were accompanied with mediastinal lymph node dissection (R2a). Partial resection without lymph node dissection was performed in 6 patients (R0). Overall 5-year survival was 24.7%. Four-year or over survivor were 4 patients who underwent a lobectomy with R2a. The patients undergoing lobectomy had a significantly better prognosis compared with patients with partial resection (p<0. 05). The patients with R2a had significantly less local recurrence than patients with R1 or R0 (p<0.05). We conclude that lobectomy with R2a is suitable treatment for metastatic lung cancer.     

Contribution of nicotinic receptors to the function of synapses in the central nervous system: the action of choline as a selective agonist of alpha 7 receptors

The alpha 7-nicotinic receptor (nAChR)-selective agonist choline and nAChR-subtype-selective antagonists led to the discovery that activation of both alpha 7 and alpha 4 beta 2 nAChRs located in CA1 interneurons in slices taken from the rat hippocampus facilitates the tetrodotoxin (TTX)-sensitive release of gamma-aminobutyric acid (GABA). Experiments carried out in cultured hippocampal neurons not only confirmed that preterminal alpha 7 and alpha 4 beta 2 nAChRs modulate the TTX-sensitive release of GABA, but also demonstrated that evoked release of GABA is reduced by rapid exposure of the neurons to acetylcholine (ACh, 10 microM-1 mM) in the presence of the muscarinic receptor antagonist atropine (1 microM). This effect of ACh, which is fully reversible and concentration-dependent, is partially blocked by superfusion of the cultured neurons with external solution containing either the alpha 7-nAChR-selective antagonist methyllycaconitine (MLA, 1 nM) or the alpha 4 beta 2-nAChR-selective antagonist dihydro-beta-erythroidine (DH beta E, 100 nM). A complete blockade of ACh-induced reduction of evoked release of GABA was achieved only when the neurons were perfused with external solution containing both MLA and DH beta E, suggesting that activation of both alpha 7 and alpha 4 beta 2 nAChRs modulates the evoked release of GABA from hippocampal neurons. Such mechanisms may account for the apparent involvement of nAChRs in the psychological effects of tobacco smoking, in brain disorders (e.g., schizophrenia and epilepsy), and in physiological processes, including cognition and nociception.     

Biology of chronic radiation effect on tissues and wound healing

Radiation therapy exerts both acute and chronic effects on normal tissue included within treatment fields. The physics of radiation therapy and treatment techniques to minimize deleterious effects of radiation are presented. Management of radiation-damaged skin is discussed. Radiation effect on tissue, wound healing, and tumorigenesis also are reviewed.     

Metabolic responses to preexercise meals containing various carbohydrates and fat

Renal function was examined after unilateral release, bilateral release or unilateral release and contralateral nephrectomy in three groups of rats following 24 h of bilateral ureteral obstruction (BUO). Excretion of water, sodium and urea was significantly greater in rats with unilateral release of BUO than in a single kidney of rats with bilateral release of BUO, in spite of similar levels of glomerular filtration rate (GFR) and effective renal plasma flow. Rats with unilateral release of obstruction and contralateral nephrectomy had a significantly lower GFR than the other two groups. These rats also responded with greater increases in fractional sodium and water excretion to the administration of exogenous atrial peptide. The results demonstrate a marked compensatory increase in sodium and water excretion in rats with unilateral release of the obstruction which serves to maintain homeostasis of fluid and salt. They also suggest a possible influence of the continuously obstructed kidney on the function of the postreleased kidney. The results also provide experimental support for a greater recovery of renal excretory function after bilateral release of obstruction.