UMLS:C0023380 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0023380 (lethargy)
5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Table salt can now be fortified with iodine and iron without interaction and without loss of potency. According to Levente Diosady, professor of Food Engineering at the University of Toronto, the amounts of the two micronutrients available to the human body have been significantly reduced when the two interacted. In the new technology, the iodine is covered with a dextrin (a water soluble starch) capsule that serves as a physical barrier to the iron. Micronutrient Initiative (an international secretariat based at IDRC that works to eliminate health problems resulting from iron, iodine, and vitamin A deficiencies) and IDRC supported the development of the technology. The efficiency of absorption of the two micronutrients in the new double fortified salt in the human body is being tested at the Hospital for Sick Children in Toronto. Later testing will be conducted by University of Ghana scientists in IDRC-funded trials that will focus on women and their families in areas of Ghana where these deficiencies are endemic. Iodine is part of thyroid hormone, which contributes to brain development in the fetus and regulates human metabolism; iodine deficiency is the most frequent cause of preventable mental retardation. Related disorders include lethargy, physical disabilities, goiter, stillbirth, and neonatal death. Iron deficiency, the most common nutritional problem in the world (particularly among women, infants, and children), is associated with anemia, fatigue, learning problems, pregnancy complications, premature births, and maternal mortality. The two deficiencies together affect more than one-third of the world's population. Approximately 1.6 billion people, in more than 100 countries, live in areas where iodine is not available in sufficient amounts; those most at risk include about one-third of China's population. It is also a severe problem in the Himalayas, the Andes, India, and West Africa.
...
PMID:Micronutrient deficiencies. Reports from the field -- Africa. 1229 Mar 27

Each year, measles kills more than 1 million children in developing countries, especially malnourished children and children with complications. Prompt hospital admission is required to prevent measles-associated deaths if children with measles exhibit a general danger sign (lethargy or unconsciousness, convulsions, inability to eat or drink, or vomiting), signs of xerophthalmia, deep or extensive mouth ulcers, severe pneumonia, severe dehydration, or severe malnutrition. No drug can treat this viral infection; measles management consists of treating complications. Health workers must insert a nasogastric tube to administer liquid foods and fluids in children with severe measles who cannot eat. They should clean both eyes with a clean cloth and water 3 times a day. They should apply tetracycline eye ointment 3 times a day for 7 days. They should give a child with signs of xerophthalmia a treatment dose of vitamin A and another dose 3 weeks later. Health workers need to clean the mouth with clean water and a pinch of salt at least 4 times a day and put 1% gentian violet on mouth sores after cleaning. They should treat an anaerobic mouth infection, indicated by a foul smelling discharge, with metronidazole. Measles patients with an acute ear infection should receive paracetamol for pain and fever and an antibiotic for the infection. In the case of ear discharge, the health worker must clean the ears at least twice a day with cotton wool or a clean cloth. They should encourage mothers of measles patients with diarrhea to continue breast feeding. Health workers must administer more fluids than usual. They need to monitor hospitalized children to detect any additional complications. They need to look for danger signs; record the child's temperature, pulse, and respiratory rate twice a day; and weigh the child daily. Children with measles must be isolated for 4 days after onset of the rash. Any child in contact with the ill child should receive a dose of measles vaccine if he/she has not already been vaccinated or had measles. A vaccine coverage rate of at least 90% is the best way to prevent measles and measles-associated deaths.
...
PMID:Preventing measles deaths. 1229 69

This paper outlines methods of therapy utilizing newer combinations of estrogens and progestins. The specific agent and length of treatment depends on the extent of disease, severity of symptoms, presence of infertility and response to pseudopregnancy. Structural formulas for 19 synthetic preparations are shown. Of 36 patients with proven endometriosis in which pseudopregnancy was induced by the use of these newer agents, satisfactory objective in 82%. Pregnancy occurred later in 6 of 10 patients who had previously been infertile and wished to become pregnant. The optimum maintenance dose is 4-6 mg of chlormadinone acetate or ethnodiol diacetate with .2 mg of mestranol and 5-10 mg of megestrol acetate with .2 mg of ethniyl estradiol. Dosage is increased only when break through bleeding occurs. Gain in weight occurred in almost 1/2 of the patients. The decidual reaction was just as great as that produced formerly by large doses of Enovid. In a more recent study 60 patients were treated with Norlestrin, 20 with Lyndiol and 20 with Ovral. Satisfactory objective and subjective remissions were obtained in 89%. Pregnancy has occurred subsequently in 17 to 43 patients who desired pregnancy. All infants have been normal. The optimum maintenance doses seem to be 10-15 mg if Norlestrin, 2.5-5 mg Lyndiol or .5-1 mg of Ovral. The most common side effect was weight gain in 35%. These agents may be used prior to conservative surgery in order to soften areas of fibrotic endometriosis or to pinpoint areas otherwise overlooked. The length of preoperative treatment depends on the extent of disease, 6 weeks being usual. The indication for prolonged pseudopregnancy is recurrent endometriosis following surgery, also proven vaginal endometriosis. Subsequent to conservative surgery, 12 to 24 weeks of therapy are given in order to inhibit ovulation and prevent reactivation of any remaining areas of endometriosis. Tables show commercial combinations and dosage regimens. Nausea, break through bleeding, breast soreness, acne, water retention, isoninia, irritability, lethargy, headaches or development of leiomyomas are side effects to be dealt with by modifying the treatment. Thromboembolic disease has not been a complication in over 500 patients but should be looked for as it has been reported by others. The effect of long-term use of these drugs has been shown to be entirely reversible without subsequent deleterious effects. Severe hepatic disease or previous mammary carcinoma are contraindications. Excessive side effects may necessitate other treatment but the newer drugs reduce this chance. The diagnosis of endometriosis should first be proven.
...
PMID:Newer synthetic progestins for the treatment of endometriosis. 1233 29

The guidance in this report is for evaluation and treatment of patients with complications from smallpox vaccination in the preoutbreak setting. Information is also included related to reporting adverse events and seeking specialized consultation and therapies for these events. The frequencies of smallpox vaccine-associated adverse events were identified in studies of the 1960s. Because of the unknown prevalence of risk factors among today's population, precise predictions of adverse reaction rates after smallpox vaccination are unavailable. The majority of adverse events are minor, but the less-frequent serious adverse reactions require immediate evaluation for diagnosis and treatment. Agents for treatment of certain vaccine-associated severe adverse reactions are vaccinia immune globulin (VIG), the first-line therapy, and cidofovir, the second-line therapy. These agents will be available under Investigational New Drug (IND) protocols from CDC and the U.S. Department of Defense (DoD). Smallpox vaccination in the preoutbreak setting is contraindicated for persons who have the following conditions or have a close contact with the following conditions: 1) a history of atopic dermatitis (commonly referred to as eczema), irrespective of disease severity or activity; 2) active acute, chronic, or exfoliative skin conditions that disrupt the epidermis; 3) pregnant women or women who desire to become pregnant in the 28 days after vaccination; and 4) persons who are immunocompromised as a result of human immunodeficiency virus or acquired immunodeficiency syndrome, autoimmune conditions, cancer, radiation treatment, immunosuppressive medications, or other immunodeficiencies. Additional contraindications that apply only to vaccination candidates but do not include their close contacts are persons with smallpox vaccine-component allergies, women who are breastfeeding, those taking topical ocular steroid medications, those with moderate-to-severe intercurrent illness, and persons aged < 18 years. In addition, history of Darier disease is a contraindication in a potential vaccinee and a contraindication if a household contact has active disease. In the event of a smallpox outbreak, outbreak-specific guidance will be disseminated by CDC regarding populations to be vaccinated and specific contraindications to vaccination. Vaccinia can be transmitted from a vaccinee's unhealed vaccination site to other persons by close contact and can lead to the same adverse events as in the vaccinee. To avoid transmission of vaccinia virus (found in the smallpox vaccine) from vaccinees to their close contacts, vaccinees should wash their hands with warm soapy water or hand rubs containing > or = 60% alcohol immediately after they touch their vaccination site or change their vaccination site bandages. Used bandages should be placed in sealed plastic bags and can be disposed of in household trash. Smallpox vaccine adverse reactions are diagnosed on the basis of clinical examination and history, and certain reactions can be managed by observation and supportive care. Adverse reactions that are usually self-limited include fever, headache, fatigue, myalgia, chills, local skin reactions, nonspecific rashes, erythema multiforme, lymphadenopathy, and pain at the vaccination site. Other reactions are most often diagnosed through a complete history and physical and might require additional therapies (e.g., VIG, a first-line therapy and cidofovir, a second-line therapy). Adverse reactions that might require further evaluation or therapy include inadvertent inoculation, generalized vaccinia (GV), eczema vaccinatum (EV), progressive vaccinia (PV), postvaccinial central nervous system disease, and fetal vaccinia. Inadvertent inoculation occurs when vaccinia virus is transferred from a vaccination site to a second location on the vaccinee or to a close contact. Usually, this condition is self-limited and no additional care is needed. Inoculations of the eye and eyelid require evaluation by an ophthalmologist and might require therapy with topical antiviral or antibacterial medications, VIG, or topical steroids. GV is characterized by a disseminated maculopapular or vesicular rash, frequently on an erythematous base, which usually occurs 6-9 days after first-time vaccination. This condition is usually self-limited and benign, although treatment with VIG might be required when the patient is systemically ill or found to have an underlying immunocompromising condition. Infection-control precautions should be used to prevent secondary transmission and nosocomial infection. EV occurs among persons with a history of atopic dermatitis (eczema), irrespective of disease severity or activity, and is a localized or generalized papular, vesicular, or pustular rash, which can occur anywhere on the body, with a predilection for areas of previous atopic dermatitis lesions. Patients with EV are often systemically ill and usually require VIG. Infection-control precautions should be used to prevent secondary transmission and nosocomial infection. PV is a rare, severe, and often fatal complication among persons with immunodeficiencies, characterized by painless progressive necrosis at the vaccination site with or without metastases to distant sites (e.g., skin, bones, and other viscera). This disease carries a high mortality rate, and management of PV should include aggressive therapy with VIG, intensive monitoring, and tertiary-level supportive care. Anecdotal experience suggests that, despite treatment with VIG, persons with cell-mediated immune deficits have a poorer prognosis than those with humoral deficits. Infection-control precautions should be used to prevent secondary transmission and nosocomial infection. Central nervous system disease, which includes postvaccinial encephalopathy (PVE) and postvaccinial encephalomyelitis (or encephalitis) (PVEM), occur after smallpox vaccination. PVE is most common among infants aged < 12 months. Clinical symptoms of central nervous system disease indicate cerebral or cerebellar dysfunction with headache, fever, vomiting, altered mental status, lethargy, seizures, and coma. PVE and PVEM are not believed to be a result of replicating vaccinia virus and are diagnoses of exclusion. Although no specific therapy exists for PVE or PVEM, supportive care, anticonvulsants, and intensive care might be required. Fetal vaccinia, resulting from vaccinial transmission from mother to fetus, is a rare, but serious, complication of smallpox vaccination during pregnancy or shortly before conception. It is manifested by skin lesions and organ involvement, and often results in fetal or neonatal death. No known reliable intrauterine diagnostic test is available to confirm fetal infection. Given the rarity of congenital vaccinia among live-born infants, vaccination during pregnancy should not ordinarily be a reason to consider termination of pregnancy. No known indication exists for routine, prophylactic use of VIG in an unintentionally vaccinated pregnant woman; however, VIG should not be withheld if a pregnant woman develops a condition where VIG is needed. Other less-common adverse events after smallpox vaccination have been reported to occur in temporal association with smallpox vaccination, but causality has not been established. Prophylactic treatment with VIG is not recommended for persons or close contacts with contraindications to smallpox vaccination who are inadvertently inoculated or exposed. These persons should be followed closely for early recognition of adverse reactions that might develop, and clinicians are encouraged to enroll these persons in the CDC registry by calling the Clinician Information Line at 877-554-4625. To request clinical consultation and IND therapies for vaccinia-related adverse reactions for civilians, contact your state health department or CDC's Clinician Information Line (877-554-4625). Clinical evaluation tools are available at http.//www.bt.cdc.gov/agent/smallpox/vaccination/clineval. Clinical specimen-collection guidance is available at http://www.bt.cdc.gov/agent/smallpox/vaccination/vaccinia-specimen-collection.asp. Physicians at military medical facilities can request VIG or cidofovir by calling the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) at 301-619-2257 or 888-USA-RIID.
...
PMID:Smallpox vaccination and adverse reactions. Guidance for clinicians. 1261 10

Sodium azide is a white crystalline solid used in the manufacture of the explosive lead azide. It is the principal chemical used to generate nitrogen gas in automobile safety airbags and airplane escape chutes and is a broad-spectrum biocide used in both research and agriculture. Toxicology and carcinogenicity studies were conducted by administering sodium azide (greater than 99% pure) in distilled water by gavage to groups of male and female F344/N rats once daily, 5 days per week for 14 days, 13 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium and Chinese hamster ovary cells. 14-Day Studies: Rats received 0, 5, 10, 20, 40, or 80 mg/kg sodium azide. All male and female rats receiving 40 or 80 mg/kg and two of five female rats receiving 20 mg/kg died during the first week of the studies. Clinical findings of toxicity included lethargy and inactivity. No grossly observable lesions were present in any of the dose groups. 13-Week Studies: Rats received 0, 1.25, 2.5, 5, 10, or 20 mg/kg sodium azide. Seven of 9 males and all 10 females receiving 20 mg/kg died before the end of the studies. Final mean body weights of treated rats were within 10% of those of the controls. Compound-related clinical findings of toxicity in the 20 mg/kg dose groups included lethargy and labored breathing. Histopathologic lesions induced by sodium azide were limited to the brain (necrosis of the cerebrum and thalamus) and lung (congestion, hemorrhage, and edema), and were observed in rats receiving 20 mg/kg that died during the studies. Body Weights, Feed Consumption, and Survival in the 2-Year Studies: Because compound-related deaths were observed in the groups receiving 20 mg/kg in the 13-week studies, lower dose levels were used in the 2-year studies. Two-year studies were conducted by administering 0, 5, or 10 mg/kg sodium azide to groups of 60 male and 60 female rats. Dose-related depression in mean body weight was observed throughout the study period. Mean feed consumption values in low- and high-dose groups were lower than control values. Survival of high-dose rats of each sex was significantly (P<0.05) lower than controls (males-control, 24/60; low-dose, 27/60; high-dose, 9/60; females-37/60; 43/60; 21/59). The reduced survival was attributed to brain necrosis and cardiovascular collapse induced by sodium azide. Neoplastic and Nonneoplastic Effects in the 2-Year Studies: There were no compound-related increases in incidences of neoplasms in rats. Significantly decreased incidences were observed for certain neoplasms, including mononuclear cell leukemia in male rats (control, 33/60; low-dose, 28/60; high-dose, 14/60), adrenal gland pheochromocytoma in male rats (26/55; 16/56; 6/54), mammary gland fibroadenoma in female rats (20/60; 11/60; 8/59), and pituitary gland neoplasms in female rats (37/60; 28/60; 17/59). These decreases reflected to some extent, but could not be attributed solely to, the reduced survival of the high-dose groups. Compound-related nonneoplastic brain lesions (necrosis of the cerebrum and thalamus) were observed at significantly (P<0.001) increased incidences in high-dose male and female rats. The increased incidence of lung congestion observed in this dose group was considered due to cardiovascular collapse secondary to brain necrosis. Genetic Toxicology: Sodium azide was mutagenic in Salmonella typhimurium strains TA100 and TA1535, with or without exogenous metabolic activation (S9); it was not mutagenic in strain TA1537 or TA98. In cytogenetic tests with Chinese hamster ovary cells, sodium azide induced sister chromatid exchanges, but not chromosomal aberrations, in the presence and the absence of S9. Conclusions: Under the conditions of these 2-year gavage studies, there was no evidence of carcinogenic activity of sodium azide in male or female F344/N rats administered 5 or 10 mg/kg. Sodium azide induced necrosis in the cerebrum and the thalamus of the brain in both male and female rats. Synonyms: Azide, Azium, Smite
...
PMID:NTP Toxicology and Carcinogeneis Studies of Sodium Azide (CAS: 26628-22-8) in F344 Rats (Gavage Studies). 1263 70

Tribromomethane, a chemical intermediate and solvent, has been identified as a drinking water contaminant resulting from water chlorination. Toxicology and carcinogenesis studies were conducted by administering tribromomethane (95%-97% pure) in corn oil by gavage to groups of F344/N rats and B6C3F1 mice of each sex once or for 14 days, 13 weeks, or 2 years. Single-Administration, Fourteen-Day, and Thirteen-Week Studies: All rats that received 2,000 mg/kg and 3/5 males and 3/5 females that received 1,000 mg/kg tribromomethane died before the end of the single-administration studies. All mice that received 2,000 mg/kg, 4/5 males and 2/5 females that received 1,000 mg/kg, and 1/5 males that received 500 mg/kg died before the end of the studies. Shallow breathing was observed for rats and male mice that received 1,000 or 2,000 mg/kg tribromomethane. In the 14-day studies, all rats that received 600 or 800 mg/kg and 1/5 males that received 400 mg/kg tribromomethane died before the end of the studies. The final mean body weight of male rats that received 400 mg/kg was 14% lower than that of vehicle controls. One of five male mice that received 600 mg/kg and 1/5 female mice that received 800 mg/kg died before the end of the studies. Final mean body weights of dosed and vehicle control mice were comparable. None of the rats died before the end of the 13-week studies (doses ranged from 12 to 200 mg/kg). Final mean body weights were comparable for dosed and vehicle control rats. All male rats that received 100 or 200 mg/kg tribromomethane and all female rats that received 200 mg/kg were lethargic. The incidences of cytoplasmic vacuolization of hepatocytes in dosed male rats were slightly increased compared with that in vehicle controls. The severity of this lesion was increased in the 200 mg/kg group. One of 10 female mice that received 100 mg/kg tribromomethane died before the end of the 13-week studies. The final mean body weight of mice that received 400 mg/kg was 8% lower than that of vehicle controls for males and was comparable to that of vehicle controls for females. Cytoplasmic vacuolization of hepatocytes was observed in the liver of 5/10 male mice that received 200 mg/kg and in 8/10 male mice that received 400 mg/kg tribromomethane. Based on these results, 2-year studies of tribromomethane were conducted by administering 0, 100, or 200 mg/kg tribromomethane in corn oil by gavage, 5 days per week for 103 weeks, to groups of 50 F344/N rats of each sex and 50 female B6C3F1 mice. Male B6C3F1 mice were administered 0, 50, or 100 mg/kg tribromomethane on the same schedule. Body Weights and Survival in the Two-Year Studies: Mean body weights of high dose male and female rats were 10%-28% lower than those of vehicle controls throughout the second year of the studies. Survival of the high dose group of male rats was significantly lower than that of the vehicle controls after week 91; no significant differences in survival were observed between any groups of female rats (male: vehicle control, 34/50; low dose, 30/50; high dose, 11/50; female: 34/50; 28/50; 28/50). Reduced survival for male rats given 200 mg/kg tribromomethane lowered the sensitivity of this group to detect a carcinogenic response. Mean body weights of dosed and vehicle control male mice were comparable throughout the study. Mean body weights of dosed female mice were 5%-16% lower than those of vehicle controls from week 28 to the end of the study. No significant differences in survival were observed between any groups of male mice; the survival of both dosed groups of female mice was significantly lower than that of the vehicle controls after week 77 (male: 41/50; 37/50; 36/50; female: 25/49; 15/50; 20/50). Reduced survival in all groups of female mice was partly due to a utero-ovarian infection; nonetheless, survival of all groups of female mice was at least 50% by week 92. Nonneoplastic and Neoplastic Effects in the Two-Year Studies: Uncommon adenomatous polyps or adenocarcinomas (combined) of the large intestine (colon or rectum) were induced in three male ratarge intestine (colon or rectum) were induced in three male rats (vehicle control, 0/50; low dose, 0/50; high dose, 3/50) and in nine female rats (0/50; 1/50; 8/50); the historical incidence of neoplasms of the large intestine is less than 0.2&percnt; in approximately 2,000 corn oil vehicle control male F344/N rats, and none has been observed in approximately 2,000 corn oil vehicle control female F344/N rats. Three of the neoplasms of the large intestine (one in the high dose male rats and two in the high dose female rats) were adenocarcinomas. Focal or diffuse fatty change of the liver was observed at increased incidences in dosed rats (male: 23/50; 49/50; 50/50; female: 19/50; 39/49; 46/50). Active chronic inflammation was observed at increased incidences in dosed male and high dose female rats (male: 0/50; 29/50; 23/50; female: 9/50; 8/49; 27/50). The incidence of necrosis of the liver was increased in high dose male rats (7/50; 3/50; 20/50) and decreased in dosed females (11/50; 3/49; 2/50). Mixed cell focus was observed at increased incidences in dosed female rats (8/50; 25/49; 28/50). Other nonneoplastic lesions observed at increased incidences in dosed rats included chronic active inflammation and squamous metaplasia of the ducts of the salivary gland (squamous metaplasia-- male: 0/50; 15/50; 31/48; female: 0/49; 10/49; 16/50; chronic active inflammation--male: 0/50; 16/50; 25/48; female: 0/49; 9/49; 18/50), squamous metaplasia of the prostate gland (2/49; 6/46; 12/50), ulcers of the forestomach (male: 1/49; 5/50; 10/50), and chronic active inflammation of the lung (male: 1/50; 7/50; 15/50). Pigmentation of the spleen was also observed at an increased incidence in high dose female rats. The salivary gland and lung lesions were characteristic of infection by rat coronavirus, a virus to which a positive serologic reaction was observed early in the studies. The incidence of follicular cell hyperplasia of the thyroid gland was increased in high dose female mice (5/49; 4/49; 19/47), and fatty change of the liver was increased in both dosed groups of female mice (1/49; 9/50; 24/50). No chemically related adverse effects were observed in male mice. Neoplastic lesions that occurred at lower incidences in dosed animals compared with those in vehicle controls included preputial gland neoplasms in male rats (10/41; 5/38; 1/34), uterine stromal polyps in female rats (10/49; 9/50; 2/50), anterior pituitary gland adenomas in male and female rats (male: 12/50; 12/48; 2/45; female: 29/48; 12/46; 16/48), mammary gland fibroadenomas in female rats (22/50; 17/50; 6/50), and alveolar/bronchiolar neoplasms in male mice (11/50; 7/50; 2/49). Other than concomitant decreases in body weights, no other reasons are obvious to correlate these decreases with chemical administration. Genetic Toxicology: Tribromomethane exhibited equivocal mutagenicity in Salmonella typhimurium strain TA100 in the absence of exogenous metabolic activation and in strains TA97 and TA98 when exposure occurred in the presence of hamster S9; tribromomethane produced no increases in revertant colonies in TA1535 or TA1537 with or without exogenous metabolic activation. Tribromomethane induced trifluorothymidine (Tft) resistance in mouse L5178Y cells with and without metabolic activation. When tested incultured Chinese hamster ovary (CHO) cells for cytogenetic effects, tribromomethane produced an increase in both sister chromatid exchanges (SCEs) and chromosomal aberrations in the absence, but not in the presence, of exogenous metabolic activation. Tribromomethane caused sex-linked recessive lethal mutations in Drosophila when administered to adult males by feeding; no induction of mutations was observed when tribromomethane was administered by abdominal injection. Results of tests for reciprocal translocations in adult male Drosophila exposed to tribromomethane by feeding were negative. In vivo tests for cytogenetic effects in bone marrow cells of male B6C3F1 mice demonstrated that intraperitoneal injection of tribromomethane induced an increase in SCEs but no increase in chromosomal aberrations. Intraperitoneal injection of tribromomethane also induced an increase in the incidence of micronucleated polychromatic erythrocytes in the bone marrow of B6C3F1 mice. Audit: The data, documents, and pathology materials from the 2-year studies of tribromomethane have been audited. The audit findings show that the conduct of the studies is documented adequately and support the data and results given in this Technical Report. Conclusions: Under the conditions of these 2-year gavage studies, there was some evidence of carcinogenic activity of tribromomethane for male F344/N rats and clear evidence of carcinogenic activity for female F344/N rats, based on increased incidences of uncommon neoplasms of the large intestine. Reduced survival for male rats given 200 mg/kg tribromomethane lowered the sensitivity of this group to detect a carcinogenic response. Chemically related nonneoplastic lesions included fatty change and active chronic inflammation of the liver in male and female rats, minimal necrosis of the liver in male rats, and mixed cell foci of the liver in female rats. There was no evidence of carcinogenic activity for male B6C3F1 mice given 50 or 100 mg/kg tribromomethane or for female B6C3F1 mice given 100 or 200 mg/kg; male mice might have been able to tolerate a higher dose. Survival of female mice was reduced, partly due to a utero-ovarian infection. Synonym: bromoform
...
PMID:NTP Toxicology and Carcinogenesis Studies of Tribromomethane (Bromoform) (CAS No. 75-25-2) in F344/N Rats and B6C3F1 Mice (Gavage Studies). 1270 34

The December 2002 COM. A 19-year-old healthy male fell into stagnant water of the intercostal waterway (salt water of South Florida), following a jet ski accident. He sustained minor superficial injuries but engulfed significant quantities of water and sediment. A few days later he developed bifrontal headaches, vomiting, a stiff neck and a temperature of 102 degrees F. A CT scan on admission without contrast was negative. The CSF had markedly elevated white count but bacterial and fungal cultures were negative. He became progressively lethargic. On the fifth day he developed seizure activity. He expired the next day despite antibiotics. Gross examination of the brain at autopsy revealed edema, cerebellar tonsillar herniation and purulent meningitis. Microscopic examination revealed a massive leptomeningeal inflammatory infiltrate composed of neutrophils, lymphocytes, and numerous histiocyte-like cells. The inflammatory infiltrate extended into the cerebral parenchyma in numerous areas also involving the cerebellum, brainstem and ventricular system. Given the exposure to stagnant water (later confirmed to be a man-made fresh water lake), and the numerous histiocytic-like cells, suspicion for an amebic etiology of the disease process was raised and the CDC identified the ameba as Naegleria Fowleri. Infection by Naegleria Fowleri, a free-living ameba, occurs after exposure to polluted water in man-made fresh water lakes, ponds, swimming pools, particularly during the warm weather months when the thermophilic ameba grows well. The pathologic substrate of the infection is an acute hemorrhagic, necrotizing meningo-encephalitis mainly at the base of the brain, brainstem and cerebellum occurring in young, healthy individuals.
...
PMID:December 2002: 19-year old male with febrile illness after jet ski accident. 1274 79

Bromodichloromethane (99% pure), one of several trihalomethanes commonly formed after chlorination of water, was selected for study because no carcinogenicity data were available for this compound and because chloroform, a related trihalomethane, had been found to cause tumors in rodents. The general population might be exposed to bromodichloromethane in drinking water supplies, in swimming pools, and in a variety of food substances. Single-administration, 14-day, 13-week, and 2-year studies were conducted in F344/N rats and B6C3F1 mice. The chemical was administered by gavage in corn oil because human exposure is primarily oral. Additional studies were performed to evaluate the potential for genetic damage in bacteria and mammalian cells. Results of the Short-Term Studies: In the single-administration studies, the chemical was administered at doses of 150-2,500 mg/kg per day. All rats and female mice at 1,250 and 2,500 mg/kg and all male mice at 600, 1,250, and 2,500 mg/kg died; 2/5 male rats, 1/5 female rats, and 2/5 female mice at 600 mg/kg died; all animals at lower dose levels survived. In the 14-day studies, rats received doses of 38-600 mg/kg, and mice received doses of 19-300 mg/kg per day. One female rat at 38 mg/kg and one female rat at 600 mg/kg died. Weight loss or decreased weight gain was seen at 300 and 600 mg/kg in male and female rats. All male mice at 150 and 300 mg/kg died, and one female mouse at 300 mg/kg died; no weight effects were observed in surviving mice. Dose-related necropsy findings included reddened renal medullae in male rats at 600 mg/kg and in male mice at 150 and 300 mg/kg. Clinical signs seen in high dose groups after dosing were hyperactivity in rats and lethargy in mice. In the 13-week studies, male and female rats received doses of 19-300 mg/kg per day, male mice received doses of 6.25-100 mg/kg per day, and female mice received doses of 25-400 mg/kg per day. Five of 10 male rats and 2/10 female rats at 300 mg/kg died. None of the mice died. Final body weights of male and female rats at 150 and 300 mg/kg were lower than those of vehicle controls (45%-88% of vehicle control weights); final body weights of male mice at 100 mg/kg and female mice at 400 mg/kg were 92% and 94% of those of the vehicle controls. Centrilobular degeneration in the liver and degeneration and necrosis of the kidney were seen in male rats at 300 mg/kg; centrilobular degeneration was seen in female rats at 300 mg/kg; degeneration andnecrosis of the kidney were seen in male mice at 100 mg/kg, and centrilobular degeneration of the liver was seen in female mice at 200 and 400 mg/kg. Experimental Design of the Two-Year Studies: The 2-year toxicology and carcinogenesis studies of bromodichloromethane were conducted by administering the chemical in corn oil by gavage, 5 days per week for 102 weeks, to groups of 50 male and female rats at doses of 0, 50, or 100 mg/kg per day; to groups of 50 male mice at doses of 0, 25, or 50 mg/kg per day; and to groups of 50 female mice at doses of 0, 75, or 150 mg/kg per day. The study in male rats was restarted because at 10.5 months into the original study, a temperature elevation killed 45/50 vehicle control male rats. Survival and Body Weight in the Two-Year Studies: Final survival of dosed rats was comparable to that of vehicle controls (male: vehicle control, 28/50; low dose, 36/50; high dose, 28/50; female: 34/50; 27/50; 41/50). Mean body weights of high dose male and female rats were decreased during the last 1.5 years of the study; final mean body weights of high dose male and female rats were 88% and 79% of the vehicle control mean weights. Final mean body weights of low dose male and female rats were comparable to those of the vehicle controls. Final survival of dosed male mice was comparable to that of the vehicle controls (34/50; 32/50; 42/50). At week 84, survival of female mice was greater than 50% in all dose groups. After week 84, survival of dosed and vehicle control female mice was reduced (final survival: 26/50; 13/50; 15/50), and this decreased survival was ass6/50; 13/50; 15/50), and this decreased survival was associated with ovarian abscesses (8/50; 19/47; 18/49). The final mean body weight of high dose male mice was 95&percnt; that of the vehicle controls; the final mean body weight of low dose male mice was comparable to that of the vehicle controls. Mean body weights of the high dose female mice were decreased during the last 1.5 years of the study; the final mean body weight was 75&percnt; that of the vehicle controls. The final mean body weight of the low dose female mice was 91&percnt; that of the vehicle controls. Nonneoplastic Effects in the Two-Year Studies: Compound-related nonneoplastic lesions included cytomegaly and tubular cell hyperplasia of the kidney and necrosis and fatty metamorphosis of the liver in male rats; eosinophilic cytoplasmic change, clear cell change, focal cellular change, and fatty metamorphosis of the liver and tubular cell hyperplasia of the kidney in female rats; fatty metamorphosisof the liver, renal cytomegaly, and follicular cell hyperplasia of the thyroid gland in male mice; and follicular cell hyperplasia of the thyroid gland in female mice. Neoplastic Effects in the Two-Year Studies: Bromodichloromethane caused compound-related increases in the incidences of neoplasms of the large intestine and kidney in male and female rats, the kidney in male mice, and the liver in female mice, as shown in the table (see page 5 of the Technical Report). The neoplasms of the large intestine and kidney are uncommon tumors in F344/N rats and B6C3F1 mice. Administration of bromodichloromethane was also associated with a decrease in the tumors of the adrenal glands in male rats, the pituitary and mammary glands in female rats, and the pituitary gland in female mice. Genetic Toxicology: Bromodichloromethane was not mutagenic in Salmonella typhimurium strains TA98, TA100, TA1535, or TA1537 when tested by the preincubational protocol at concentrations up to 1,000 ug/plate with or without metabolic activation. The compound was not mutagenic in the mouse lymphoma L5178Y/TK± assay in the presence of S9 but did induce forward mutations in the system in the presence of metabolic activation from rat liver S9. Cytogenetic tests with Chinese hamster ovary cells demonstrated no induction of chromosomal aberrations orsister chromatid exchanges following treatment with bromodichloromethane in either the presence or absence of metabolic activation. Data Audit: An audit of the experimental data was conducted for the 2-year toxicology and carcinogenesis studies of bromodichloromethane. No discrepancies were found that influenced the final interpretations of the results of these studies. Conclusions: Under the conditions of these 2-year gavage studies, there was clear evidence of carcinogenic activity for male and female F344/N rats and B6C3F1 mice as shown by increased incidences of tubular cell adenomas and adenocarcinomas in the kidney and adenocarcinomas and adenomatous polyps in the large intestine in male and female rats, increased incidences of tubular cell adenomas and adenocarcinomas in the kidney of male mice, and increased incidences of hepatocellular adenomas and carcinomas in female mice. Synonym: dichlorobromoethane
...
PMID:NTP Toxicology and Carcinogenesis Studies of Bromodichloromethane (CAS No. 75-27-4) in F344/N Rats and B6C3F1 Mice (Gavage Studies). 1274 32

The infectivity and pathogenicity of newly discovered baculovirus, CuniNPV (family Baculoviridae, genus Nucleopolyhedrovirus) originally isolated from the mosquito Culex nigripalpus Theobald, was evaluated in laboratory bioassys against thirteen species and four genera of mosquitoes native to the northeastern U.S. Purified virus at a dosage rate of 1.6 x 10(7) occlusion bodies/ml with 10 mM Mg2+ added was used in exposures with second through fourth instars at temperatures ranging from 17 to 27 degrees C. High infection rates and accompanying mortality were achieved in Cx. pipiens L. (83.0-14.4%), Cx. pipiens f. molestus (80.4% infection), and Cx. salinarius Coquillett (48.0-43.1%). Cx. restuans Theobald was also susceptible but infection rates were lower (21.3-12.5%). The gross pathology associated with infection was identical to that reported in Cx. nigripalpus. Infected larvae were lethargic and were often suspended at the water surface. Development of CuniNPV was observed in the nuclei of the midgut epitheial cells in the gastric caeca and posterior region of the stomach of host larvae. One hundred percent mortality was observed in all larvae that exhibited gross symptoms of infection within 4-d p.i. Cx. territans Walker (subgenus Neoculex Dyar) was the only Culex mosquito that was not susceptible. No infections were obtained with any species of Aedes [Ae. vexans (Meigen)], Culiseta [Culiseta morsitans (Theobald)] or Ochlerotatus [Ochlerotatus canadensis (Theobald), Oc. cantator (Coquillett), Oc. communis (De Geer), Oc. excrucians (Walker), Oc. japonicus (Theobald), Ochlerotatus stimulans (Walker), and Ochlerotatus triseriatus (Coquillett)]. The host range of CuniNPV appears to be restricted to Culex mosquitoes within the subgenus Culex. An inhibitory effect on transmission of CuniNPV was observed when a liver powder/Brewer's yeast mixture was used as a source of food reinforcing the critical role of Mg2+ and sensitivity of the infection process to the presence other divalent cations (Cu2+, Fe2+, and Zn2+) in the larval medium that interfered with the infection process. The high infectivity and pathogenicity of CuniNPV for the principal vectors of West Nile virus in North America make CuniNPV an attractive candidate for future development as a biopesticide.
...
PMID:Infectivity and pathogenicity of a novel baculovirus, CuniNPV from Culex nigripalpus (Diptera: Culicidae) for thirteen species and four genera of mosquitoes. 1468 Jan 19

Butanal oxime is used as a volatile antiskinning agent in paints, inks, and similar products. Butanal oxime was chosen for toxicology testing as a representative of the aldoxime class. Male and female F344/N rats and B6C3F1 mice received butanal oxime (99 percent pure) in drinking water for 15 days or by gavage in 0.5 percent methylcellulose for 14 weeks. Animals were evaluated for clinical pathology, reproductive system effects, and histopathology. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, and mouse peripheral blood erythrocytes. In the 15-day studies, groups of five male and five female rats and mice received 0, 312, 625, 1,250, 2,500, or 5,000 ppm butanal oxime in drinking water, resulting in average daily doses of approximately 40, 70, or 100 mg butanal oxime/kg body weight to male and female rats; 45, 90, 130, 200, or 300 mg/kg to male mice; and 45, 85, 100, 130, or 170 mg/kg to female mice. Due to body weight loss and lack of water consumption, all male and female rats receiving 2,500 or 5,000 ppm were removed from the study on day 9; average daily doses were not calculated for these groups. All other rats and mice survived until the end of the studies. Mean body weights of 1,250 ppm male and female rats and 2,500 and 5,000 ppm male and female mice were significantly less than those of the controls. Male mice receiving 5,000 ppm and females receiving 2,500 or 5,000 ppm lost weight during the study. Water consumption by rats and mice receiving 1,250 ppm or greater was less than that by the controls. Thinness in 2,500 and 5,000 ppm rats and mice was the only clinical finding of toxicity. Spleen weights were significantly decreased in 2,500 and 5,000 ppm female mice. No chemical-related lesions were observed grossly; histologic examinations were not performed. In the 14-week studies, groups of 10 male and 10 female rats and mice received butanal oxime by gavage at doses of 0, 25, 50, 100, 200, or 600 mg/kg, 5 days per week for 14 weeks. All 600 mg/kg rats died or were killed moribund during the first week of the study; in the 600 mg/kg mouse groups, seven males and nine females died, were killed moribund, or were killed accidentally before the end of the study. Mean body weights of 100 and 200 mg/kg male rats, 600 mg/kg male mice, and female mice administered 50 mg/kg or greater were less than those of the controls. Clinical findings of toxicity in 600 mg/kg rats included loss of coordination, wobbly gait, shaking, blinking, constant grooming and scratching of the face, head weaving, burying of the face in bedding, lethargy, and prostration; in 600 mg/kg mice, clinical findings included ataxia, loss of balance after rearing, squinting, and burying of the face in the bedding. Hematology results of the 14-week gavage studies indicate that butanal oxime induces a methemoglobinemia and a responsive anemia in rats and mice. Spleen weights of 100 and 200 mg/kg male rats, female rats administered 50 mg/kg or greater, and 200 and 600 mg/kg male mice were increased, as were the liver weights of 200 mg/kg female rats and mice. In animals that died early due to butanal oxime administration, hepatocellular necrosis was the primary pathologic finding. Degeneration of the nasal olfactory epithelium was observed in dosed rats and mice that died early as well as in animals that survived to the end of the studies. Additional chemical-related nasal findings were respiratory epithelial changes in male rats and suppurative exudate in male and female mice. Increased incidences and/or severities of splenic hematopoietic cell proliferation and pigmentation (hemosiderin) as well as bone marrow hyperplasia were also observed in dosed groups, particularly in the 200 and 600 mg/kg groups, and were indicative of erythrocyte damage. Butanal oxime (3 to 10,000 ug/plate) was mutagenic in S. typhimurium strain TA1535 in the presence of 5 percent or 10 percent rat liver S9; an equivocal response was seen in TA100 with 30 percent rat S9, and no mutagenic activity was seen in TA98, with or without rat or hamster liver S9. Butanal oxime induced chromosomal aberrations in cultured Chinese hamster ovary cells, with and without S9. Significant increases in the frequencies of micronucleated normochromatic erythrocytes were observed in vivo in peripheral blood of male and female mice administered 25 to 600 mg/kg butanal oxime for 14 weeks by gavage. Synonyms: Butanaloxime; butylaldoxime; butyraldehyde oxime; n-butyraldehyde oxime; butyraldoxime; n-butyraldoxime Trade names: Exkin 1, Exkin No. 1 Anti-Skinning Agent, Skino #1, Troykyd Anti-Skin BTO
...
PMID:NTP technical report on the toxicity studies of Butanal oxime (CAS No. 110-69-0) administered in drinking water and by gavage to F344/N rats and B6C3F1 mice. 1501 36

<< Previous 1 2 3 4 5 6 7 8 9 10