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At least 127 records · Page 7Linked to original sources
PubMed2004

Demographic, pathologic, and toxicological profiles of 127 decedents testing positive for ephedrine alkaloids.

The relative toxicity of ephedra-containing dietary supplements is disputed. In order to ascertain the magnitude of the problem, we reviewed all autopsies in our Medical Examiner's jurisdiction, from 1994 to 2001, where ephedrine or any its isomers (E+) were detected. Toxicology testing results were tabulated and anatomic findings in E+ cases were compared to those in a control group of drug-free trauma victims. Of 127 E+ cases identified, 33 were due to trauma. Decedents were mostly male (80.3%) and mostly Caucasian (59%). Blood ephedrine concentrations were <0.49 mg/l in 50% of the cases, range 0.07-11.73 mg/l in trauma victims, and 0.02-12.35 mg/l in non-trauma cases. Norephedrine (NE) was present in the blood of 22.8% (mean of 1.81 mg/l, S.D.=3.14 mg/l) and in the urine of 36.2% (mean of 15.6 mg/l, S.D.=21.50mg/l). Pseudoephedrine (PE) was present in the blood of 6.3% (8/127). More than 88% (113/127) of the decedents also tested positive for other drugs, the most common being cocaine (or its metabolites) and morphine. The most frequent pathologic diagnoses were hepatic steatosis (27/127) and nephrosclerosis (22/127). Left ventricular hypertrophy was common, and coronary artery disease (CAD) detected in nearly one third of the cases. The most common findings in E+ deaths are those generally associated with chronic stimulant abuse, and abuse of other drugs was common in those with CAD. There were no cases of heat stroke or rhabdomyolysis. In most cases, norephedrine was not detected, suggesting it plays no role in ephedrine toxicity.

Adolescent↗
PubMed1992

Effect of graded concentrations of gossypol on calf performance: toxicological and pathological considerations.

The effects of feeding diets containing 0, 100, 200, 400, or 800 ppm of free gossypol were examined in 60 Holstein bull calves from 1 to 120 d of age. The concentrations of free gossypol were varied by varying amounts of cottonseed meals from three different sources. Cottonseed meal totaled 31% of each treatment ration. Feed consumption, BW, and blood parameters were collected on all calves at 30-d intervals throughout the trial. There were no significant differences between the groups for feed consumption, BW, or average daily gain. Changes in the group means for hematology and chemistry variables examined were modest and insufficient to distinguish diagnostically between safe and unsafe free gossypol concentrations for the different groups. Clinical evidence of disease was limited to the calves fed 400 or 800 ppm of free gossypol after 90 d of age. One calf in the group fed 400 ppm and 4 in the group fed 800 ppm died as a result of circulatory failure associated with gossypol consumption. We conclude from this study that a ration containing up to 200 ppm of free gossypol is safe, 400 ppm of free gossypol is toxic, and 800 ppm of free gossypol results in death losses. These results are compatible with previously reported naturally occurring toxicological outbreaks.

Animal Feed↗
PubMed2006

Mitochondrial glutathione transport: physiological, pathological and toxicological implications.

Although most cellular glutathione (GSH) is in the cytoplasm, a distinctly regulated pool is present in mitochondria. Inasmuch as GSH synthesis is primarily restricted to the cytoplasm, the mitochondrial pool must derive from transport of cytoplasmic GSH across the mitochondrial inner membrane. Early studies in liver mitochondria primarily focused on the relationship between GSH status and membrane permeability and energetics. Because GSH is an anion at physiological pH, this suggested that some of the organic anion carriers present in the inner membrane could function in GSH transport. Indeed, studies by Lash and colleagues in isolated mitochondria from rat kidney showed that most of the transport (>80%) in that tissue could be accounted for by function of the dicarboxylate carrier (DIC, Slc25a10) and the oxoglutarate carrier (OGC, Slc25a11), which mediate electroneutral exchange of dicarboxylates for inorganic phosphate and 2-oxoglutarate for other dicarboxylates, respectively. The identity and function of specific carrier proteins in other tissues is less certain, although the OGC is expressed in heart, liver, and brain and the DIC is expressed in liver and kidney. An additional carrier that transports 2-oxoglutarate, the oxodicarboxylate or oxoadipate carrier (ODC; Slc25a21), has been described in rat and human liver and its expression has a wide tissue distribution, although its potential function in GSH transport has not been investigated. Overexpression of the cDNA for the DIC and OGC in a renal proximal tubule-derived cell line, NRK-52E cells, showed that enhanced carrier expression and activity protects against oxidative stress and chemically induced apoptosis. This has implications for development of novel therapeutic approaches for treatment of human diseases and pathological states. Several conditions, such as alcoholic liver disease, cirrhosis or other chronic biliary obstructive diseases, and diabetic nephropathy, are associated with depletion or oxidation of the mitochondrial GSH pool in liver or kidney.

Animals↗
PubMed2000

Chemical, pathological and toxicological studies of the effects of RICOM-1013-J of Ricinus communis var minor on women volunteers and rodents.

RICOM-1013-J (Ricinus communis var minor) administered orally once to each of 12 women volunteers at a dose of 2.5-2.7 g per 8 months, protected against pregnancy over a period of 7-8 months of study. A study of the effect of a contraceptive dose (20 mg/kg) on metabolic parameters in rat (food and water in-take, urine and faecal output and body weight) over a period of 4 months showed a slight decrease in all the parameters in the first 1-8 weeks. This effect was reversible attaining pretreatment levels from week 16. The LD(50) in an acute toxicity test in mice was 63.1 +/- 16.0 g/kg s.c. Determination of blood urea, sodium (Na(+)), potassium (K(+)), chloride (Cl(-)) and bicarbonate (HCO$_¿3¿ ¿-¿$)as a measure of renal function and alkaline phosphatase (ALP), transaminases (GPT and GOT) and transpeptidases (GGT) as a measure of liver function showed that liver function profiles in pretreated rats were not significantly different from control (p < 0.05) on day 21 to day 150. However, serum levels of ALP and GGT at day 120 to day 150 were moderately but significantly elevated (p > 0.05) compared with the control. There were no significant changes in renal function profiles in pretreated rats (p < 0.05) compared with the control. The results of the liver and renal function profiles in women volunteers showed that there were no significant (p < 0.05) changes in renal functions on day 206 following RICOM-1013-J administration. However, serum levels of ALP and GGT showed a slight rise in about 70% of volunteers, whereas bilirubin and transaminases levels were normal. The present results indicate a very high efficacy and margin of safety of RICOM-1013-J in women volunteers. The increase in ALP and GGT in both animal and women volunteers suggest mild intrahepatic cholestatic changes which may be attributed to an oestrogenic effect of RICOM-1013-J.

Adult↗
PubMed1994

Methylmercury poisoning: long-term clinical, radiological, toxicological, and pathological studies of an affected family.

For 3 months in 1969 a family in the United States that included a pregnant mother consumed pork containing methylmercury. Children, aged 20, 13, and 8 years and a neonate, developed severe neurological signs. Twenty-two years later, the 2 oldest had cortical blindness or constricted visual fields, diminished hand proprioception, choreoathetosis, and attentional deficits. Magnetic resonance images showed tissue loss in the calcarine and parietal cortices and cerebellar folia. The youngest had quadriplegia, blindness, and severe mental retardation until their deaths. The brain of the 8-year-old who died at age 30 showed cortical atrophy, neuronal loss, and gliosis, most pronounced in the paracentral and parietooccipital regions. The total mercury level in formalin-fixed, left occipital cortex was 1,974 ng/gm as measured by atomic absorption. Regional brain mercury levels correlated with extent of brain damage. A control patient had 38.5 ng of mercury/gm in the occipital cortex. Systemic organs in the patient and a control subject had comparable mercury levels. In mercury-intoxicated rats, we found that only 5 to 10% of total brain mercury was lost by formalin fixation. Brain inorganic mercury in the patient ranged from 82 to 100%. Since inorganic mercury crosses the blood-brain barrier poorly, biotransformation of methyl to inorganic mercury may have occurred after methylmercury crossed the blood-brain barrier, accounting for its persistence in brain and causing part of the brain damage.

Adolescent↗
PubMed1994

Pathology and toxicology of beluga whales from the St. Lawrence Estuary, Quebec, Canada. Past, present and future.

An indigenous population of 450-500 beluga whales (Delphinapterus leucas) inhabiting the St. Lawrence Estuary has been exposed chronically for more than 50 years to a complex mixture of industrial pollutants including organochlorinated compounds (OC), polycyclic aromatic hydrocarbons (PAH) and heavy metals. From 1983 to 1990, we have necropsied 45 well preserved carcasses out of a total of 120 beluga whales reported dead over this period. Of these 45 animals, nine were affected by 10 malignant neoplasms. Fifteen animals (33%) were affected by pneumonia. Milk production was compromised in eight of 17 mature females (41%), by inflammatory changes (seven animals) and cancer (one animal) which affected the mammary glands. Opportunistic bacteria were found in pure culture, and/or in significant amounts in at least two organs in 20 belugas (44%). The concentrations of both total PCBs and highly chlorinated PCB congeners were much higher in St. Lawrence animals than in Arctic beluga whales. OC-induced immunosuppression has been repeatedly demonstrated in a wide variety of animal species. Therefore, it is probable that the immune functions of St. Lawrence beluga whales are impaired. Benzo[a]pyrene adducts were detected in 10 of the 11 St. Lawrence beluga whales of which tissues (six livers, 10/11 brains) were analyzed by a method based on HPLC. No such adducts were found in four Arctic animals. Since benzo[alpha]pyrene is one of the most potent chemical carcinogens known to man, these compounds might be responsible for some of the cancers observed in that population. Overall, our findings contrast vividly with those of others who found that cancers are exceedingly rare in free-ranging odontocete populations and that the major causes for mortalities in these populations are bacteria, parasites, and trauma.

Animals↗
PubMed1988

Toxicology and pathology of methyl bromide in F344 rats and B6C3F1 mice following repeated inhalation exposure.

The toxicity of methyl bromide was studied in male and female F344 rats and B6C3F1 mice exposed by inhalation to 160 ppm methyl bromide or air 6 hr/day, 5 days/week for up to 6 weeks. The animals were killed after 3, 10, or 30 exposure days, or when 50% mortality was observed in any group. Only female rats survived the entire 30 exposure days at 160 ppm methyl bromide with less than 50% mortality. There were clear species- and sex-related differences in susceptibility of specific organs to methyl bromide. Primary target organs were the brain, kidney, nasal cavity, heart, adrenal gland, liver, and testis. In rats, neuronal necrosis occurred in the cerebral cortex, hippocampus, and thalamus of the brain whereas in mice neuronal necrosis occurred primarily in the internal granular layer of the cerebellum. Nephrosis occurred in all exposed mice, but not rats, and was likely a major cause of moribundity and death. Necrosis of the olfactory epithelium was more severe and extensive in rats than mice. Myocardial degeneration occurred in male and female rats and to a lesser degree in male mice. There was atrophy of the inner zone of the adrenal cortex in female mice and cytoplasmic vacuolation of the adrenal cortex in rats. Testicular degeneration occurred in rats and mice. The target organ specificity of methyl bromide is similar to that of methyl chloride, suggesting that the two monohalomethanes may have a common mechanism of action.

Administration, Inhalation↗
PubMed2006

Pre-clinical toxicology and pathology of 9-(2'-hydroxyethylamino)-4-methyl-1-nitroacridine (C-1748), a novel anti-cancer agent in male Beagle dogs.

We have developed a group of 4-substituted-1-nitroacridines with potent anti-tumor activity against prostate cancer and less toxic than parent 1-nitroacridines. The most active 9-(2'-hydroxyethylamino)-4-methyl-1-nitroacridine (C-1748) was selected for pre-clinical studies. The current study was undertaken to evaluate clinical and/or morphological adverse effects of C-1748 as a single intravenous dose at concentrations ranging from 0.16 to 4.6 mg/kg administered to male Beagle dogs. The maximum tolerated dose was 1.5 mg/kg. Emesis was observed in all groups lasting an average of 30 min to 12 h post-dosing. At high dose, extreme aggression was observed in one dog followed by disorientation and depression lasting for 48 h a frequent observation with chemotherapy. Reductions in platelets and white blood cells were observed which was similar to that seen with other chemotherapeutic agents. A compensatory hyperplasia of lymph nodes and a transient and limited extravasation in the intestinal mucosa were also observed. Increases in aspartate aminotransferase, alkaline phosphatase and creatine phosphokinase were transient with normal levels restored by day 9. These enzyme increases were accompanied by epithelial hypertrophy of larger bile ductules in the periportal triads of the liver. The low toxicity profile and high tumor target activity make this novel class of drug a promising chemotherapeutic agent.

Alanine Transaminase↗
PubMed2005

Human melanocyte biology, toxicology, and pathology.

The human melanocytes of the skin, hair, eyes, inner ears, and covering of the brain provide physiologic functions important in organ development and maintenance. Melanocytes develop from embryonic neural crest progenitors and share certain traits with other neural crest derivatives found in the adrenal medulla and peripheral nervous system. The distinctive metabolic feature of melanocytes is the synthesis of melanin pigments from tyrosine and cysteine precursors involving over 100 gene products. These complex biochemical mechanisms create inherent liabilities for melanocytic cells if intracellular systems necessary for compartmentalization, detoxification, or repair are compromised. Melanocyte disorders may involve pigmentation, sensory functions, autoimmunity, or malignancy. Environmental factors such as ultraviolet radiation and chemical exposures, combined with heritable traits, represent the principal hazards associated with melanocyte disorders.

Autoimmunity↗
PubMed1997

Oxidative stress and thiol depletion in plasma and peripheral blood lymphocytes from HIV-infected patients: toxicological and pathological implications.

OBJECTIVES: To determine, first, whether the plasma and lymphocytes of HIV-positive individuals and AIDS patients have alterations in the major thiols glutathione and cysteine, and/or their oxidative disulphide and mixed disulphide products; and, secondly, whether thiol/disulphide status differs in patients with sulphonamide drug hypersensitivity reactions. DESIGN: Thiols provide critical cellular defence against toxic drug reactive intermediates and endogenous oxidative stress, and may modulate HIV replication. Glutathione is reported to be low in HIV-positive individuals and AIDS patients, but this is controversial and the mechanism responsible is unknown. Also unknown is whether altered thiol/disulphide status determines the predisposition of HIV-positive and AIDS patients to drug reactions. METHODS: Thiols and disulphides were measured by high-performance liquid chromatography. RESULTS: Both plasma thiols were decreased by approximately 58% in HIV-positive individuals and AIDS patients compared with uninfected controls (P < 0.05), with increases of up to threefold in oxidized products (P < 0.05). Similarly, in lymphocytes, thiols were decreased by 30-35% (P < 0.05), with apparent increases in oxidized products. For both glutathione and cysteine, the thiol/disulphide ratios also were decreased (P < 0.05). The plasma and lymphocyte glutathione thiol/disulphide ratios were highly correlated (r = 0.7661; P = 0.0001) among all subjects. No parameters differed in patients with drug reactions, or with antiretroviral therapy. CONCLUSIONS: The enhanced thiol oxidation in HIV-positive individuals and AIDS patients indicates oxidative stress, which also contributes to thiol depletion, and may enhance damage to macromolecular targets. These mechanisms may contribute to enhanced viral replication and other pathological outcomes. HIV-positive individuals' and AIDS patients' predisposition to drug hypersensitivity reactions appears to be unrelated to thiol/disulphide status.

Analysis of Variance↗
PubMed2006

Clinical, pathological and toxicological findings of a iatrogenic selenium toxicosis case in feeder pigs.

Histopathological and toxicological analyses confirmed a clinical diagnosis of selenium (Se) intoxication in pigs from a farm in Spain. After an initial episode of diarrhoea, animals presented both dermatological and neurological signs; the most obvious sign was a marked hind limb paresis. Cutaneous lesions consisted on diffuse alopecia, multifocal skin necrosis and coronary band necrosis of the hooves. Central nervous system lesions involved the cervical and lumbar intumescences of the spinal cord and consisted of a severe, bilateral symmetrical poliomyelomalacia of the ventral horns; pons and medulla oblongata also presented lesions of polioencephalomalacia. Analyses of feed and sera from clinically affected pigs revealed a marked increase in Se concentration. Clinical investigations indicated that a failure in Se dosage in feed was the cause of the toxicosis.

Alopecia↗