Immunotoxicologic Assessment of Subacute Exposure of Rats to Carbon Tetrachloride with Comparison to Hepatotoxicity and Nephrotoxicity

Immunotoxicologic Assessment of Subacute Exposure of Rats toCarbon Tetrachloride with Comparison to Hepatotoxicity and Nephrotoxicity.SMIALOWICZ, R.J., SIMMONS, J. E., LUEBKE, R. W., AND ALLIS,J. W. (1991). Fundam. Appl. Toxicol 17, 186-196. The immunotoxicity,hepatotoxicity, and nephrotoxicity of subacute exposure to carbontetrachloride (CCI4) were evaluated in young adult (8-9 weeksold) male Fischer 344 rats dosed by gavage with CCI4 for 10consecutive days at 0, 5, 10, 20 or 40 mg/kg/day. Two days followingthe last treatment rats were evaluated for alterations in immunefunction by monitoring the following; body and lymphoid organweights; mitogen and mixed leukocyte reaction lymphoproliferativeresponses; natural killer cell activity; and cytotoxic T lymphocyteresponses. A separate group of similarly dosed rats was immunizedwith sheep red blood cells (SRBQ on Day 9 of dosing, and theprimary antibody response was assessed 4 days later. Hepaticand renal toxicity were assessed 2 days after the last treatmentby monitoring organ weights, serum indicators of hepatic andrenal damage, and hepatic cytochrome P450 levels, as well asby histological evaluation. Significant increases in relativeliver weights were observed in rats dosed at 40 mg/kg/day. Histologically,these livers displayed mild to moderate vacuolar degenerationand minimal to mild hepatocellular necrosis. In addition, serumlevels of aspartate aminotransferase and alanine aminotransferasewere elevated at this dosage, as well as at 20 mg/kg/day. Therewere no renal effects observed at these dosages of CCU. In addition,no consistent alterations were observed in the immune parametersexamined in these same animals nor in the rats immunized withSRBC. Furthermore, there was no difference in the antibody responseto SRBC in another set of rats dosed at 40, 80, or 160 mg/kg/dayCCI⁴. These results indicate that CCU is not immunotoxic inthe rat at dosages that produce overt hepatotoxicity.     

IgA and IgG Subclass Deficiency in a Poor Population in a Developing Country

The levels of IgG, IgG subclasses, IgM and IgA were determined in serum from 17 patients with IgA deficiency and severe or frequent infections, allergy and/or autoimmunity (median age 7 years, range 2–19), 11 healthy IgA-deficient adults and 35 controls (median age 7 years, range 2–19). In serum from all groups IgG, IgM and IgA antibodies were determined against β-lactoglobulin, E. coli O antigens and poliovirus type 1 antigen. In saliva of 15 IgA-deficient patients and 12 of the controls IgG, IgM and secretory component-carrying antibodies against E. coli O antigens and poliovirus type I were determined. The majority of the studied individuals lived under poor socio-economic conditions in Brazil, with consequent heavy microbial exposure. One IgA-deficient patient with rheumatoid arthritis also had IgG2 deficiency but no infectious problems. Four out of the 35 controls without any obvious infectious problems were found with IgA or IgG subclass deficiency. One of the 11 healthy IgA-deficient adults was low in the IgG2 subclass, one in IgGl and one in IgG3. Those with symptomatic IgA deficiency had significantly higher serum IgG than the controls, especially in the age group 6–11 years. This latter group also had significantly increased serum IgG 1 and IgG2 levels when compared with the age-matched controls. Salivary IgM antibodies to E. coli and poliovirus antigens were significantly higher among the symptomatic IgA-deficient individuals than among the controls. It is not clear at present whether these increased Ig levels are secondary to frequent infections and/or part of mechanisms that may compensate for the IgA deficiency.     

Endoscopic treatment of sphenoid sinusitis

Juxtaposed between the posterior nasal cavity and skull base, the diseased sphenoid sinus presents unique challenges when surgical drainage is required. Endoscopic techniques have gained widespread popularity for the treatment of sphenoid sinusitis, yet the efficacy of such treatment remains largely unknown. Thirty-four patients who underwent endoscopic sphenoidotomy were monitored over a period of 6 months to 5 years. Surgery was performed with the superior turbinate used as the key landmark for identification and enlargement of the natural sphenoid ostium. Surgical access was through either a transnasal or transethmoid approach, depending on whether disease was limited to the sphenoid sinus. Prospective analysis of 26 patients with established outcome measures demonstrated a significant reduction in facial pain, nasal drainage, and congestion 6 months after surgery (p < 0.0001). Medication use was also reduced but to a lesser extent (p < 0.05). Endoscopic sphenoidotomy appears to be a safe technique that effectively reduces patient morbidity associated with sphenoid sinusitis. (Otolaryngol Head Neck Surg 1996;114:736-44.)     

Symptomatic cysts in otherwise normal lungs of children and adults

The clinical and pathological features of 28 lung cysts resected in the period 1980-1989, excluding those from patients with emphysema elsewhere in their lungs, have been reviewed. In 12 children aged 8 days to 17 years, five cysts were congenital adenomatoid malformations, three were bronchogenic cysts, two were intralobar sequestrations, one was a cystic haemangioma and one resembled the cysts excised from 16 adult patients. This latter group ranged in age from 20 to 62 years and included 11 cigarette smokers and five asthmatics. Twelve of these cysts were intralobar and four were attached by a pedicle to the pleural surface of the lung. All these cysts had a fibromuscular wall showing varying degrees of acute and chronic inflammation. The presence of at least a partial lining of epithelial cells in all the cysts was confirmed using an immunocytochemical marker. The surrounding lung did not show any significant pathology. These cysts are labelled as simple fibromuscular pulmonary cysts. In the childhood cases, a congenital cause could be established in the majority. The pathogenesis of the adult cysts remains unclear. The presence of inflammation in the cyst walls does not necessarily suggest a role for infection, as secondary infection of cysts cannot be ruled out. An aetiological role for local damage due to cigarette smoking or asthma must be taken into consideration.     

The prevalence of childhood asthma in Costa Rica

The prevalence of asthma in children between the ages of 5 and 17 years in Costa Rica was determined using a large sample (n = 2682). The definition of asthma was based on a combination of a physician's diagnosis and a symptom score, using information from a questionnaire given to the parents. An overall asthma prevalence as high as 23·4% was found. Sex, age, urban/rural location, or rain precipitation did not show any association with the diagnosis of asthma. The presence of smokers in the home was found to be an important risk factor (odds ratio = 1·6). Another identified risk factor was a high yearly average outside temperature, i.e. above 25°C (odds ratio = 1·8). Furthermore, the proportion of children with more than four upper respiratory infections during the preceding year was found to be significantly increased in children with asthma (odds ratio = 4·3). The non-asthma group seemed to use equal amounts of drugs for the treatment of asthma as the asthma group. For a country like Costa Rica with limited economic resources the current work indicates two important issues for consideration in the future; firstly, to try to define the cause(s) of asthma and secondly, to continuously inform the physicians about the best way of diagnosing and treating asthmatic patients to ensure optimal handling of this large patient group.     

A Sensitive Method for Specific Quantitation of Secretory IgA

A method to quantitate specifically secretory IgA (SIgA) has been developed using the enzyme-linked immunosorbent assay. The IgA in the test sample was adsorbed to anti-alpha antibodies attached to plastic tubes via a cost of IgA myeloma protein. The reacted SIgA was determined using anti-secretory component antiserum conjugated with alkaline phosphatase. The technique permitted quantitation of secretory IgA in biological fluids like milk, urine, and saliva with a reproducibility of +/-7%, down to 0.03 mg/l. In contrast to earlier techniques, the presence of up to 157% of serum IgA without secretory component (SC) and free SC did not disturb the measurements of SIgA. Furthermore, variations in pH and osmolarity, within biological ranges in secretions, did not influence the estimations.     

HALOTHANE ADSORPTION COMPLICATING THE USE OF SODA-LIME TO HUMIDIFY ANAESTHETIC GASES

If tbe anaesthetic circle system is arranged to increase thehumidity of fresh anaesthetic gases by placing the carbon dioxideabsorbent canister between the fresh gas inlet and the patient,drying of the soda-lime can occur. Very dry soda-lime adsorbssignificant quantities of halothane. Using fresh soda-lime,effluent halothane concentration reached 50% of the input concentrationin 35 s, but this time increased to 500s when dry soda-limewas used The use of dry soda-lime can result in a slow inhalationinduction or in the release of adsorbed halothane during a subsequentanaesthetic.     

Alcohol and non-traffic unintended injuries

In a review of the English language literature on alcohol and unintentional injury we identified 21 studies on falls, 36 on drownings and 32 on bums from 1947-1986. The proportion of fatal and non-fatal fall victims who had been drinking ranged from 21–77%, and 18–53% respectively. In three more recent studies, 35–63% of persons fatally injured in falls had been drinking. In five other studies 13–37% of persons injured in non fatal falls had been drinking. In our earlier review of drowning studies with complete ascertainment and duration of submergence specified, 27–47% of those who drowned had positive BAC's. In eight subsequent studies, alcohol was identified in 21–47% of drowning deaths. In our earlier review alcohol was involved in 9-86% of bum deaths. In five more recent US studies, alcohol was found in 12–61 % of fatally injured burn victims. Case control studies are needed to establish whether alcohol increases the risk of trauma. Studies are also needed of interventions to reduce the proportion of these injuries where alcohol is involved.     

Oral Tolerization Leads to Active Suppression and Bystander Tolerance in Adult Rats while Anergy Dominates in Young Rats

Oral tolerance was induced in 4-week-old (young) and 12-week-old (adult) rats by feeding ovalbumin (OvA)-containing pellets during 4 weeks. Seven weeks after removal of the OvA-pellets the rats were immunized with a mixture of OvA and human serumalbumin (HSA) in Freund's complete adjuvant (FCA), and the following immune response was monitored. Both the young and adult groups of OvA-fed rats had significantly suppressed OvA-specific delayed-type hypersensitivity (DTH) responses and T-cellproliferation, reflecting a long-lasting T-cell tolerance to OvA both in vivo and in vitro. Furthermore, spleen cells from rats tolerized as adults were able to suppress the proliferation of primed T-cells from normal immunized rats, demonstrating thepresence of antigen-specific suppressive cells. Accordingly, the adult rats showed bystander suppression of the response to HSA with respect to DTH-reaction, specific proliferation, and reduced enlargement of the draining lymph nodes after immunization.There was no evidence of active suppression in vitro or bystander tolerance in the orally tolerized young group, indicating that anergy rather than active suppression was prevalent in these rats. Furthermore, in the young group there was no suppression of the antibody response since the IgG and IgE anti-OvA antibody levels were indistinguishable from those of the controls. Contrary to the young rats, the adult fed group showed transiently elevated levels of IgG anti-OvA antibodies at 1 weekpost-immunization, followed by a subsequent significantly suppressed IgG antibody response. In conclusion, the results demonstrate that the induction of anergy or active suppression after antigen feeding can be determined by the age at which the antigenis introduced to the mucosal immune system.