The use of elexacaftor/tezacaftor/ivacaftor in patients with cystic fibrosis postliver transplant: A case series.

Introduction: Cystic fibrosis (CF)-related liver disease (CFLD) manifests as a wide spectrum of hepatobiliary disease and can progress to need liver transplantation. Elexacaftor/tezacaftor/ivacaftor (elx/tez/iva) is a cystic fibrosis transmembrane conductance regulator modulator that has superior efficacy compared to previously approved modulators. Use of elx/tez/iva, should be approached with caution in individuals with CFLD or following liver transplantation due to possible increases in liver function tests (LFTs) and drug-drug interactions with several immunosuppressant medications.

Chronic inhalation toxicity and carcinogenicity study on potassium octatitanate fibers (TISMO) in rats.

A chronic inhalation toxicity/carcinogenicity study of potassium octatitanate fibers (TISMO) was conducted in male Fischer 344 rats. Groups of 135 rats were exposed via whole-body inhalation to 0, 20, 60, or 200 WHO fibers/cc of TISMO, 6 h/day, 5 days/w for 24 mo. Six of 30 subgroup rats were killed after 3, 6, 12, 18, and 24 mo of exposure for lung burden evaluations.

Hypoadrenocorticism in beagles exposed to aerosols of plutonium-238 dioxide by inhalation.

Hypoadrenocorticism, known as Addison's disease in humans, was diagnosed in six beagles after inhalation of at least 1.7 kBq/g lung of 238PuO2. Histological examination of adrenal gland specimens obtained at necropsy revealed marked adrenal cortical atrophy in all cases.

Inhalation toxicity and carcinogenicity of isoprene in rats and mice: comparisons with 1,3-butadiene.

As with 1,3-butadiene (BD), inhalation exposure of B6C3F1 mice to isoprene (2-methyl-1,3-butadiene) caused a macrocytic anemia; induced increases in sister chromatid exchanges in bone marrow cells and in levels of micronucleated erythrocytes in peripheral blood; and produced degeneration of the olfactory epithelium, forestomach epithelial hyperplasia, and testicular atrophy. Most notable was the finding that like BD, isoprene induced neoplasms in the liver, lung, Harderian gland, and forestomach of mice. The carcinogenic effects of isoprene were observed after a 26-week exposure (6 h/day, 5 days/week) of male mice to 700 ppm or higher concentrations of isoprene followed by a 26-week recovery period.

Toxicity of inhaled chloroprene (2-chloro-1,3-butadiene) in F344 rats and B6C3F(1) mice.

Chloroprene (2-chloro-1,3-butadiene) is a high production chemical used almost exclusively in the production of polychloroprene (neoprene) elastomer. Because of its structural similarity to isoprene (2-methyl-1,3-butadiene) and to 1,3-butadiene, a potent trans-species carcinogen, inhalation studies were performed on chloroprene to characterize its toxicological potential and to provide a basis for selecting exposure concentrations for chronic toxicity and carcinogenicity studies. Thirteen-week inhalation toxicology studies were conducted in male and female F344 rats and B6C3F(1) mice at exposure concentrations of 0, 5, 12, 32 or 80 ppm (6 h/day; 5 days/week).

Thirteen-week inhalation toxicity of 2- and 4-chloronitrobenzene in F344/N rats and B6C3F1 mice.

Toxicity studies were performed by exposing F344/N rats and B6C3F1 mice to 2- and 4-chloronitrobenzene (CNB) by whole-body inhalation 6 hr/day, 5 days/week, for 13 weeks. Animals were evaluated for clinical chemistry (rats), hematology (rats), histopathology, and body/organ weights. Exposure concentrations were 0, 1.

Serum and urine biochemical diversity among adult wild-caught Aotus nancymae and Saimiri peruviensis.

Serum and urine analytes were compared between adult wild-caught owl monkeys (Aotus nancymae) and adult wild-caught squirrel monkeys (Saimiri peruviensis) to determine if normative clinical pathology data were similar. An objective of the study was to confirm that species of neotropical primates are distinct with regard to physiologic parameters, and should not be considered interchangeable in biomedical research. Significant differences (P < 0.

Hematologic values of the wild-caught karyotype V owl monkey (Aotus vociferans).

Blood samples from 35 wild-caught owl monkeys (Aotus vociferans, karyotype V) were analyzed to estimate reference intervals of hematologic variables for the species. Findings indicated that distributions were abnormal for leukocytes, neutrophils, eosinophils, basophils, and monocytes. Statistically significant sex differences, too small to be of clinical importance, were found in values for mean cell hemoglobin concentration, leukocytes, and basophils.

Hepatic effects of inhaled plutonium dioxide in beagles.

The effects of inhaled 238PuO2 deposited in the liver of dogs were studied in beagles exposed to initial lung depositions ranging from 5.7 to 2979.7 Bq/g lung.

Hematological effects of inhaled plutonium dioxide in beagles.

A life-span study indicated that plutonium activity in the thoracic lymph nodes is a contributor to development of lymphopenia in beagles exposed to 239PuO2. Significant lymphopenia was found in 67 (58%) beagles given a single nose-only exposure to 239PuO2 to result in mean initial lung depositions ranging from 0.69 to 213.

Isoprene, an endogenous hydrocarbon and industrial chemical, induces multiple organ neoplasia in rodents after 26 weeks of inhalation exposure.

Isoprene, the 2-methyl analogue of 1,3-butadiene, is a high production chemical used largely in the manufacture of synthetic rubber and is the major endogenous hydrocarbon exhaled in human breath. Thirteen-week inhalation toxicology studies of isoprene were conducted in male and female F344 rats and B6C3F1 mice at exposure concentrations of 0, 70, 220, 700, 2200, and 7000 ppm (6 h/day; 5 days/week). In addition, 26-week inhalation studies at the same exposure levels, followed by a 26-week recovery period, were conducted in male rats and mice.

Serum and urine biochemical diversity among wild-caught and colony-born Aotus nancymae.

Serum and urine analytes were compared between adult wild-caught and adult colony-born owl monkeys (Aotus nancymae), to determine if normative clinical pathology data were similar. Significant differences (P < or = 0.05) were noted in serum protein, glucose, sodium, urine calcium, calcium clearance, and fractional clearance of calcium between the two groups.

Comparison of blood and urine analytes between two karyotypes of owl monkey, Aotus nancymae and Aotus vociferans.

Serum and urine analytes were compared between two karyotypes of owl monkey, Aotus nancymae and A. vociferans, to determine if normative clinical pathology data obtained from one karyotype were applicable to the other. Statistically significant differences (P < or = 0.

Urinary enzyme concentrations in the owl monkey (Aotus nancymae).

The activity of three urinary enzymes, alkaline phosphatase (ALP), aspartate aminotransferase (AST), and N-acetyl-beta-D-glucosaminidase (NAG), was evaluated in 71 adult owl monkeys. Fifty-six animals had normal renal function, while 15 had evidence of renal dysfunction. Urinary enzyme: urinary creatinine ratios (UE: UCr) were also determined.

Susceptibility of owl monkeys to Plasmodium falciparum in relation to hemoglobin and karyotype.

Humans with inherited abnormalities of hemoglobin (Hb) synthesis have less frequent and less severe infections of malaria. This study sought to determine if karyotypic variation in the owl monkey was expressed as differences in Hb moieties and if it offered a selective advantage in susceptibility to malaria. Five karyotypes of owl monkey were evaluated on the basis of the electrophoretic mobility of their major and minor Hb components.

Renal clearance and excretion of endogenous substances in the owl monkey.

The clearance and excretion of creatinine, calcium, phosphorus, sodium, and potassium by the kidney was evaluated in 62 owl monkeys using timed urine collections and quantitative urinalyses. The endogenous clearance of creatinine was determined for each monkey. Urinary electrolyte excretion and fractional electrolyte excretions (FE) were measured.

Impaired renal function in owl monkeys (Aotus nancymai) infected with Plasmodium falciparum.

Impaired renal function was observed in sixteen Aotus nancymai 25 and 3 months following infection with the Uganda Palo Alto strain of Plasmodium falciparum. Decrease were noted in the clearance of endogenous creatinine, creatinine excretion, and urine volume while increases were observed in serum urea nitrogen, urine protein, urine potassium, fractional excretion of phosphorus and potassium, and activities of urinary enzymes. The results were suggestive of glomerulonephropathy and chronic renal disease.

Protein concentration in urine of normal owl monkeys.

The excretion of urinary protein was evaluated in 62 owl monkeys using timed urine collections. The ratio of urine protein to urine creatinine concentrations (Up/c) was determined for each monkey. Linear regression analysis was used to calculate the correlation between that ratio and urine protein (mg/dl) and 24-hour urinary protein loss (mg/kg).

Total serum creatine kinase and isozyme concentrations in the owl monkey.

Serum samples from 62 owl monkeys were analyzed to determine concentrations of creatine kinase activity and isozymes. Fifty monkeys were determined to be clinically normal, while twelve had cardiac disease. Findings showed that the data had a non-normal distribution.

Serum chemistry of the wild caught karyotype I night monkey (Aotus nancymai).

Serum samples from 254 wild-caught Aotus nancymai were analyzed to determine the reference intervals for serum chemistry parameters in this species. Findings show values of total bilirubin, creatinine, alkaline phosphatase, alanine aminotransferase, urea nitrogen, serum albumin, and gamma glutamic transpeptidase having a non-normal distribution. Based on nonparametric tests, significant differences between male and female values were observed for cholesterol, serum calcium, and gamma glutamic transpeptidase.

Inhalation toxicity studies of cobalt sulfate in F344/N rats and B6C3F1 mice.

Groups of 10 F344/N rats and B6C3F1 mice of each sex were exposed to cobalt sulfate heptahydrate aerosols of 0, 0.3, 1.0, 3.

Inhalation toxicology of isoprene in F344 rats and B6C3F1 mice following two-week exposures.

Isoprene (2-methyl-1,3-butadiene) was selected for toxicologic evaluations because of its structural similarity to 1,3-butadiene, a potent rodent carcinogen. Two-week inhalation toxicology studies of isoprene were conducted in F344 rats and B6C3F1 mice at exposure concentrations of 0, 438, 875, 1750, 3500, or 7000 ppm. For rats, there were no chemically related changes in survival, body weight gain, clinical signs, hematologic or clinical chemistry parameters, or gross or microscopic lesions.

Cadmium inhalation and male reproductive toxicity.

Cadmium is a highly toxic element that is cumulative and has a long biological half-life in mammals. The severe toxicity of cadmium in man has been known for more than 100 years. Despite the knowledge that cadmium is toxic, only 20 human cases of poisoning via ingestion were recorded prior to 1941, whereas in the ensuing five-year period more than 680 cases of cadmium poisonings from accidental oral ingestion of this metal were documented.

Relationship of serum total calcium and albumin and total protein in owl monkeys (Aotus nancymai).

A positive linear relationship was found between total calcium and albumin and between total calcium and total protein in the serum of 205 owl monkeys. Adjustment formulas for calcium were derived: adjusted calcium (mg/dl) = measured calcium (mg/dl) - 0.84 [albumin (g/dl)] + 3.