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High-potency sodium fluoride: a literature review.

A considerable number of clinical studies are documented in the literature on oral products containing 5,000 ppm fluoride (F), mainly nonabrasive gels. Study results show that this level of fluoride provides marked caries protection. These high-potency gels are especially effective for irradiated head and neck cancer patients, who typically develop rampant caries. Radiation therapy causes a marked decrease in salivation (xerostomia), which predisposes the teeth to caries formation and results in devastating consequences. The currently recommended treatment for these patients involves a 2-step regimen using a 5,000 ppm F gel and a conventional 1,000 ppm F dentifrice. Unfortunately, this treatment usually results in noncompliance because two steps are inconvenient for most patients. A 5,000 ppm F dentifrice meets the oral-hygiene needs of these patients. It provides an effective level of fluoride and a convenient one-step application procedure that increases patient compliance.

Adult↗

[Total protein and immunoglobulin level in the saliva of pregnant women].

The content of total protein and immunoglobulin in the saliva of pregnant women has been determined quantitativly by the biuret-method and radial immunodiffusion. IgA has been ascertained in all samples of saliva, whereas was appears IgG in 78,55% and IgM only 52,50% of the samples. It was discussed the importance of salive-IgA during the pregnancy.

Antibody Formation↗

[Oral and rectal premedication of children with midazolam]].

Premedication in children continues to be a problem in anaesthesiology. Apart from the application of premedication drugs, a strongly committed anaesthetist and sound psychological work are decisive prerequisites for adequate premedication. In this randomized study, 329 children aged between 1 and 14 who were scheduled for small surgical procedures were examined. Based on the results of a preliminary trial using different dosages of midazolam, the children were premedicated either orally with 0.4 mg/kg BW midazolam or with 0.3 mg/kg BW midazolam as a rectal solution and the premedication effect was recorded according to the classification of Lindgren. These reduced doses of midazolam, which were much lower than those described in the literature, led to very good premedication effects, too. Regarding cardiovascular behaviour, an increasing anxiolysis and the effect of premedication led to a significant decline in mean arterial blood pressure and heart frequency. The circulatory changes that occurred were at no time clinically relevant in any child, and therefore no treatment was needed. Based on the measured oxygen saturation, no significant respiratory changes were seen during the observation period. The frequency and extent of the registered side-effects were classified as slight. Side-effects such as singultus, salivation and ataxia/gesticulations were of no danger during the entire perioperative period.

Adjuvants, Anesthesia↗

Tick removal.

Many methods of tick removal that have been reported in the literature have proved to be unsatisfactory in controlled studies. Some methods may even cause harm by inducing the tick to salivate and regurgitate into the host. Ticks are best removed as soon as possible, because the risk of disease transmission increases significantly after 24 hours of attachment. The use of a blunt, medium-tipped, angled forceps offers the best results. Following tick removal, the bite area should be inspected carefully for any retained mouthparts, which should be excised. The area is then cleaned with antiseptic solution, and the patient is instructed to monitor for signs of local or systemic illness. Routine antibiotic prophylaxis following tick removal generally is not indicated but may be considered in pregnant patients or in areas endemic to tick-borne disease.

Animals↗

Neuroleptic malignant syndrome due to olanzapine.

Neuroleptic malignant syndrome (NMS) is a rare and potentially fatal complication precipitated by the use of antipsychotic medications, most notably haloperidol. Criteria previously described include: exposure to the neuroleptic class of medications; hyperthermia; muscle rigidity; a cluster of laboratory and physical findings that may include mental status changes, autonomic instability, creatine phosphokinase elevation and leukocytosis, and exclusion of other causes for the patient's condition. A prodrome of mental status changes, autonomic instability, tremors, diaphoresis, excess salivation, and extrapyramidal signs may precede NMS. Prior reports of NMS linked to olanzapine have been in patients who had been previously treated with other neuroleptic agents or in patients who had previous episodes of NMS precipitated by other neuroleptics. Several cases included patients treated with olanzapine in addition to another neuroleptic. This report describes a case of NMS associated with olanzapine in a patient who had not previously been exposed to the neuroleptic drug class. At the time this patient presented, there were no reports in the literature of NMS associated with olanzapine alone. Treatment of NMS includes: immediate withdrawal of all neuroleptics; supportive care; fever control; management of autonomic instability (tachycardia, tachypnea, blood pressure fluctuations); and pharmacologic management with dantrolene and bromocriptine.

Adult↗

Observations on the feeding behaviour of Paratrichodorus anemones in relation to tobravirus transmission.

Feeding by P. anemones, an efficient vector of tobacco rattle virus (TRV), was investigated by video-enhanced interference light microscopy. Four stages were observed after transfer of individual nematodes, extracted from soil, to Nicotiana tabacum seedling roots in agar: i) acclimatisation; ii) approach and scrutiny; iii) preparation; and iv) feeding. Prior to commencement of stage 'iv' about 4 cells perforated by rapid onchiostyle thrusting remained alive, each having been almost immediately abandoned by the nematode. During the stage iv) approximately 5% of perforated cells remained alive. Feeding on individual cells was similar to that previously reported for Trichodorus similis: cells from which cytoplasm was ingested after a prolonged period of salivation were invariably killed, with adjacent cells being unaffected. During feeding a number of cells perforated but soon afterwards abandoned by P. anemones remained alive, providing an effective pathway for successful transmission of TRV to plants by the nematode.

Animals↗

NTP Toxicology and Carcinogenesis Studies 2-Butoxyethanol (CAS NO. 111-76-2) in F344/N Rats and B6C3F1 Mice (Inhalation Studies).

2-Butoxyethanol is a member of a family of ethylene glycol monoalkyl ethers. It is used extensively as a solvent in surface coatings such as lacquers, enamels, varnishes, and latex paint; in paint thinners, paint stripping formulations, and inks; and in degreasers and industrial and household cleaners. 2-Butoxyethanol was nominated for study because of its widespread use in industrial and consumer applications, the potential for exposure to workers and the general population, and the absence of chronic toxicity data. Male and female F344/N rats and B6C3F1 mice were exposed to 2-butoxyethanol (greater than 99% pure) by inhalation (primary route of human exposure) for 14 weeks or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, and the bone marrow of male F344/N rats and B6C3F1 mice. 14-WEEK STUDY IN RATS: Groups of 10 male and 10 female rats were exposed to 2-butoxyethanol by inhalation at concentrations of 0, 31, 62.5, 125, 250, or 500 ppm, 6 hours per day, 5 days per week for 14 weeks. One female rat in the 250 ppm group was killed moribund during week 8; four females in the 500 ppm group were killed moribund during week 1 and one during week 5. Final mean body weights of females exposed to 500 ppm were significantly less than those of the chamber controls. Clinical findings included abnormal breathing, pallor, red urine stains, nasal and eye discharge, lethargy, and increased salivation and/or lacrimation. Due to vascular thrombosis and infarction in the tail vertebrae of 500 ppm female rats, the tails became necrotic and either sloughed off or were chewed off. The primary effect on the hematopoietic system was an anemia characterized as macrocytic, normochromic, and regenerative in males exposed to 125 ppm or greater and, to a greater extent, in all exposed groups of females. Compared to the chamber controls, kidney weights of males exposed to 500 ppm and females exposed to 125 ppm or greater and liver weights of males exposed to 250 or 500 ppm and females exposed to 125 ppm or greater were significantly increased, and thymus weights of females exposed to 500 ppm were significantly less. In female rats killed moribund, there was considerable histologic evidence of thrombosis in tissues and organs including the nasal cavity, incisors, liver, lung, and heart. In addition to thrombosis, infarction occurred in the vertebrae of the tail resulting in necrosis and loss of the distal portion of the tail. There were also inflammation, necrosis, and ulceration of the forestomach; necrosis and centrilobular degeneration of the liver; renal tubule degeneration; and atrophy of the spleen and thymus. Exposure-related increases in the incidences of Kupffer cell pigmentation, forestomach inflammation and epithelial hyperplasia, bone marrow hyperplasia, splenic hematopoietic cell proliferation, and renal tubule pigmentation were observed in male and/or female rats surviving to the end of the study. 14-WEEK STUDY IN MICE: Groups of 10 male and 10 female mice were exposed to 2-butoxyethanol by inhalation at concentrations of 0, 31, 62.5, 125, 250, or 500 ppm, 6 hours per day, 5 days per week for 14 weeks. Two male and two female mice exposed to 500 ppm died and two males and two females were killed moribund during the first 2 weeks of the study. Final mean body weights of 125, 250, and 500 ppm male mice were significantly less than those of the chamber controls. Clinical findings were observed only in 500 ppm males and females that died or were killed moribund and included abnormal breathing, red urine stains, and lethargy. Hematologic evaluation indicated an anemia that was characterized as normocytic, normochromic, and regenerative in mice exposed to 62.5 ppm or greater; the anemia was more pronounced in females. Liver weights of males exposed to 500 ppm were significantly greater than the chamber controls. In mice either dying early or killed moribund, there were inflammation, necrosis, and ulceration of the forestomach; mediastinal pleura and peritoneal inflammationmmation associated with the forestomach lesions; liver necrosis; renal tubule degeneration; atrophy of the spleen, thymus, and mandibular and mesenteric lymph nodes; and degeneration of the testis. Exposure-related increases in the incidences of hematopoietic cell proliferation and hemosiderin pigmentation of the spleen, Kupffer cell hemosiderin pigmentation of the liver, inflammation and epithelial hyperplasia of the forestomach, and renal tubule hemosiderin pigmentation occurred in male and/or female mice surviving to the end of the study. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were exposed to 2-butoxyethanol by inhalation at concentrations of 0, 31.2, 62.5, or 125 ppm, 6 hours per day, 5 days per week for 104 weeks. For hematology and bone marrow analyses, additional groups of 27 male and 27 female rats were exposed to 0, 62.5, or 125 ppm for evaluation at 3, 6, and 12 months and nine male and nine female rats were exposed to 31.2 ppm for evaluation at 3 (hematology only) and 6 months. Survival and Body Weights: Survival of exposed male and female rats was similar to the chamber control groups. The mean body weights of females exposed to 125 ppm were generally less than the chamber control group. Hematology and Bone Marrow Cellularity: The most consistent exposure-related effect on the hematopoietic system was an exposure concentration-related mild macrocytic, normochromic, regenerative anemia present at 3, 6, and 12 months, with females more affected than males. Significant increases in bone marrow cellularity and decreases in the myeloid/erythroid ratio relative to the chamber controls were observed at all time points in females exposed to 125 ppm, and a decrease in the myeloid/erythroid ratio was observed in males exposed to 125 ppm at 12 months. Pathology Findings: The incidence of benign or malignant pheochromocytoma (combined) of the adrenal medulla in females exposed to 125 ppm was not significantly increased compared to the chamber controls but exceeded the historical control range. Exposure-related increases in the incidences of hyaline degeneration of the olfactory epithelium and Kupffer cell pigmentation of the liver were observed in male and female rats. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female mice were exposed to 2-butoxyethanol by inhalation at concentrations of 0, 62.5, 125, or 250 ppm, 6 hours per day, 5 days per week for 104 weeks. For hematology and bone marrow analyses, additional groups of 30 male and 30 female mice were exposed to 0, 62.5, 125, or 250 ppm for evaluation at 3, 6, and 12 months. Survival and Body Weights: Survival of male mice exposed to 125 or 250 ppm was significantly less than that of the chamber control group. The mean body weights of exposed males were generally less than those of the chamber control group during the last 6 months of the study. The mean body weights of exposed female mice were less than those of the chamber control group; the reductions were greater and occurred earlier than those observed in males. Hematology: The most consistent exposure-related effect on the hematopoietic system was an exposure concentration-related minimal normocytic, normochromic, regenerative anemia present at 3, 6, and 12 months, with females affected slightly more than males. Pathology Findings: In females exposed to 250 ppm, incidences of forestomach squamous cell papilloma and squamous cell papilloma or carcinoma (combined) were significantly increased relative to the chamber controls, and these incidences exceeded the ranges in historical chamber controls. In 2-butoxyethanol exposed males, there were possible exposure-related increases in the incidences of squamous cell papilloma of the forestomach, although the increases were not significant and the incidences were within the historical control range for chamber controls. Accompanying these neoplasms in females and, to a lesser extent, in males were exposure-related increases in the incidences of ulcer and epithelial hyperplasia of the forestomach. In male mice exposed to 250 ppm, the incidence of hemangiosarcoma of the liver was significantly increased relative to chamber controls and exceeded the range in historical controls; in addition, there were possible exposure-related increases in the incidence of hepatocellular carcinoma. Incidences of hemosiderin pigmentation in the Kupffer cells were significantly increased in 125 and 250 ppm males and all exposed groups of females. The incidences of splenic hematopoietic cell proliferation and hemosiderin pigmentation were generally increased in males and females, and the incidences of bone marrow hyperplasia were increased in males. The incidences of hyaline degeneration of the olfactory and respiratory epithelia of the nose were increased in female mice. GENETIC TOXICOLOGY: 2-Butoxyethanol did not induce mutations in any of the S. typhimurium strains tested, with or without induced hamster or rat liver S9. 2-Butoxyethanol induced cycle delay but did not induce either sister chromatid exchanges or chromosomal aberrations in cultured Chinese hamster ovary cells with or without S9. 2-Butoxyethanol did not induce micronuclei in bone marrow cells of male rats or mice administered the chemical by intraperitoneal injection three times at 24-hour intervals. CONCLUSIONS: Under the conditions of these 2-year inhalation studies, there was no evidence of carcinogenic activity of 2-butoxyethanol in male F344/N rats exposed to 31.2, 62.5, or 125 ppm. There was equivocal evidence of carcinogenic activity of 2-butoxyethanol in female F344/N rats based on the increased combined incidences of benign or malignant pheochromocytoma (mainly benign) of the adrenal medulla. There was some evidence of carcinogenic activity of 2-butoxyethanol in male B6C3F1 mice based on increased incidences of hemangiosarcoma of the liver. A marginal increase in the incidences of forestomach squamous cell papilloma and an increase in the incidences of hepatocellular carcinoma may have been exposure related. There was some evidence of carcinogenic activity of 2-butoxyethanol in female B6C3F1 mice based on increased incidences of fore stomach squamous cell papilloma or carcinoma (mainly papilloma). Increased incidences of forestomach neoplasms in male and female mice occurred in groups in which ulceration and hyperplasia were also present. Exposure to 2-butoxyethanol caused a mild regenerative anemia and effects secondary to the anemia. Synonyms: 2-Butoxy-1-ethanol; m-butyl ether; butyl glycol; ethylene glycol monobutyl ether Trade name: Butyl Cellosolve

Journal Article↗

[Dyspnea analyse and treatment to adult acute epiglottitis].

OBJECTIVE: To discuss the estimation and treatment of adult acute epiglottitis dyspnea. METHOD: 126 adult with acute epiglottitis patients were analyzed. RESULT: None of 30 patients undergone epiglotiotomy had asphyxia, inflammation diffuse or serious hemorrhage. 8 patients undergone tracheotomy, one patient undergone thyroericotomy but died. One of 87 patients with conservative treatment died. CONCLUSION: Gaspping, salivating and dyslogia are symbols of severe larynx obstruction. Fibrous laryngoscope is the best way of examine. Keeping respiratory path open and eliminating epiglottis swelling is the key of treatment.

Acute Disease↗

Noma (cancrum oris): case report in a 4-year-old HIV-positive South African child.

Cancrum oris (noma) is a gangrenous infection that develops in the mouth and spreads rapidly to other parts of the face. The disease occurs mostly in conditions of poverty, poor hygiene and malnutrition. In sub-Saharan Africa the frequency in several countries is estimated to be 1-7 cases per 1,000 population, and as many as 12 cases per 1,000 in the most affected communities. About 90% of these children die without receiving any care, yet the disease can, and should, be prevented. With increasing numbers of children who are malnourished and who have compromised immune systems (compounded by the HIV pandemic) the prevalence of conditions such as noma is likely to increase. Among the earliest features of noma are excessive salivation, marked fetor oris, facial oedema and a greyish-black discolouration of the skin in the affected area. This devastating gangrenous lesion may involve the cheek, the chin, the infra-orbital margin, palate, nose, antrum and virtually any part of the face. This report describes a 4-year-old HIV-positive African girl, who was abandoned, discharged from the Plastics Unit and now lives in a child care sanctuary. Little is known about her history prior to her arrival at the home a few weeks previously. The clinical examination revealed a delay in growth and physical development equivalent to that of a 2-year-old child. The left cheek had a perforating ulcer in a healing phase. The perforation, about 1 cm in diameter, was surrounded by oedematous tissues showing a mild to moderate erythema. The peripheral oedema extended to the lower palpebral, the upper labial, left labial commissural, mandibular and pre-parotid regions. Submental, submandibular and cervical lymph nodes were mildly painful upon palpation. The child was not pyretic. The intra-oral examination revealed the features of acute necrotising gingivitis (ANG). ANG was generalised and showed classic interdental crater-like ulcers covered with whitish debris. Halitosis was pronounced. Examination of the second quadrant revealed a large ulcer extending from the distal aspect of the deciduous canine to the distal aspect of the second deciduous molar. The adjacent palatal mucosa was severely oedematous. The alveolar bone supporting the first and the second molars was completely exposed to the fundus of the vestibulum. It was not possible to obtain intraoral photographs or radiographs. Chlorhexidine gluconate (0.2% solution) and metronidazole tablets, 200 mg twice daily for 15 days were prescribed. The child was seen every alternate day for 10 days and her condition improved rapidly. Halitosis had subsided. She was then referred to the Johannesburg Hospital for further treatment under general anaesthesia. The proposed treatment plan was as follows: removal of dental accretions and polishing of all teeth, extraction of the left maxillary teeth supported by non-vital bone, resection of the necrotic bone in the left maxilla and reconstructive surgery in the left cheek.

AIDS-Related Opportunistic Infections↗

[Acceptance of van Swieten's liquor in Japan].

Carl Peter Thunberg, a Swedish medical doctor and botanist who visited Japan in 1775 as a medical doctor attached to the Dutch Trade House in Dejima, Nagasaki, taught the treatment of syphilis using mercury water to Japanese doctors and interpreters. This therapy is based on the oral administration of a 0.014% solution of mercuric chloride and was published in 1754 by Gerard van Swieten in Vienna, who questioned the utility of the conventional salivation therapy. The dose was set taking safety into account. Kogyu Yoshio, a Japanese-Dutch interpreter, had already read about it in a book written by J. J. Plenck, when he was taught about the therapy by Thunberg. He recorded Thunberg's teachings in his book "Komohijiki", presenting details of various formulations, including a high-dose formulation. The mercury therapy was subsequently spread across the country by medical doctors who learned Western medicine through the Dutch. In the 1820's, Genshin Udagawa, who read a number of Western medical books, published books on Western drugs. In these books, G. Udagawa included precise information on "Swieten Yakushu-hu (medicated alcohol)", including information on the dosage, formulation, mode of usage, and precautions for use. The maximum dose of mercuric chloride established chloride established by van Swieten was included in the Japanese Pharmacopoeia up to its 5th edition.

Alcohols↗

An overview of herbal supplement utilization with particular emphasis on possible interactions with dental drugs and oral manifestations.

Herbal medication in the United States is a popular form of therapy. This paper provides an overview of the utilization of herbal supplements with particular emphasis on possible interactions with oral health drugs and oral manifestations. Herbal supplements are regulated by the Dietary Supplement Health and Education Act (DSHEA), which limits their regulation by the U.S Food and Drug Administration (FDA). A number of studies indicate that there is a progressive increase in the utilization of herbal supplements. The majority of consumers of these products are white, middle-aged women who have some college education. Many of the consumers use pharmaceutical drugs concurrently, but most do not inform their health-care providers about their use of herbal supplements. Various herbal supplements have been reported or are suspected to interact with certain oral health drugs, the most important one being 1) bromelain, cayenne, chamomile, feverfew, dong quai, eleuthro/Seberian ginseng, garlic, ginkgo, ginger, ginseng and licorice interacting with aspirin; 2) aloe latex, ephedra, ginseng, rhubarb, cascara sagrada, licorice, and senna interacting with corticosteriods; 3) kava, St. John's wort, chamomile, and valerian interacting with central nervous system (CNS) depressant drugs; and 4) herbs acting on the gastrointestinal system, altering the absorption of several orally administered drugs. Further, the use of some herbal supplements has been reported to be associated with oral manifestations, including aphthous ulcers, lip and tongue irritation, and swelling with feverfew; gingival bleeding with feverfew and ginkgo; tongue numbness with echinacea; xerostomia with St. John's wort; oral and lingual dyskinesia with kava; and salivation with yohimbe. These potential effects of herbal supplements in conjunction with factors related to regulation restrictions suggest that the use of these products may be associated with various adverse reactions that can affect oral health and treatment. Dental hygienists should inform themselves about herbal supplements in order to offer appropriate oral health care to individuals who take these substances.

Blood Coagulation↗

NTP Toxicology and Carcinogenesis Studies of 2-Mercaptobenzothiazole (CAS No. 149-30-4) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

Toxicology and carcinogenesis studies of technical-grade 2-mercaptobenzothiazole (96%-97% pure), a rubber accelerant and preservative, were conducted by administering the chemical by gavage in a corn oil vehicle to groups of F344/N rats and B6C3F1 mice of each sex for 16 days, 13 weeks, or 2 years. 2-Mercaptobenzothiazole was nominated for study by the National Institute of Environmental Health Sciences and the National Institute for Occupational Safety and Health. Sixteen-Day and Thirteen-Week Studies: In 16-day studies, mean body weight gains of rats receiving 2,500 mg/kg were 6-7 g lower than those of vehicle controls; 4/5 male and 5/5 female mice dosed with 3,000 mg/kg and 4/5 female mice dosed with 1,500 mg/kg died; lethargy and prostration occurred in most of these animals after gavage. Based on these results, doses were selected for both species in the 13-week studies were 0, 94 (mice only), 188, 375, 750, and 1,500 mg/kg. In the 13-week studies, no chemical-related deaths occurred in rats, but body weight gains in males dosed with 1,500 mg/kg and in females dosed with 750 or 1,500 mg/kg were lower than those in the vehicle control groups. Hepatomegaly occurred at the two highest doses in males and at all doses in females; however, no microscopic pathologic changes were noted in any tissue. More than half the mice dosed with 1,500 mg/kg died, but no compound-related body weight changes occurred. Clinical signs in mice were dose related and included lethargy in animals dosed with 375 mg/kg and lacrimation, salivation, and clonic seizure in some dosed with 750 or 1,500 mg/kg. No association between these clinical signs of toxicity and gross or microscopic pathologic effects were observed. Doses selected for the 2-year studies were 0, 375, and 750 mg/kg for male rats and for mice of each sex and 0, 188, or 375 mg/kg for female rats. Body weight and Survival in the Two-Year Studies: Fifty animals of each species and sex were administered 2-mercaptobenzothiazole in corn oil by gavage 5 days per week for 103 weeks. Administration of 2-mercaptobenzothiazole resulted in decreased survival in dosed male rats (vehicle control, 42/50; low dose, 22/50; high dose, 20/50) and in the high dose group of female mice (37/50; 39/50; 22/50) but not in female rats (28/50; 31/50; 25/50) or in male mice (38/50; 33/50; 30/50). No effect on body weight gain in dosed rats was observed; in dosed mice, minor reductions occurred between weeks 3 and 64, withrecovery thereafter. Postgavage lethargy and prostration occurred frequently in dosed rats and mice. Nonneoplastic and Neoplastic Effects in the Two-Year Studies: The severity of nephropathy was increased in dosed male rats. Ulcers and inflammation of the forestomach were prevalent in dosed rats, as were increased incidences of epithelial hyperplasia and hyperkeratosis in male rats, but no neoplasms of the forestomach were observed. There were no increases of nonneoplastic lesions in mice which were considered to be compound related. The incidences of a variety of tumors were increased in rats dosed with 2-mercaptobenzothiazole; some of the increased incidences were not dose related. In low dose male rats, increased incidences (P<0.01) were observed for mononuclear cell leukemia (7/50; 16/50; 3/50) and pancreatic acinar cell adenomas (2/50; 13/50; 6/49). Increased tumor incidences with dose-related trends (P<0.05) included pituitary gland adenomas in females (15/49; 24/50; 25/50), preputial gland adenomas or carcinomas (combined) in males (1/50; 6/50; 5/50), adrenal gland pheochromocytomas or malignant pheochromocytomas (combined) in males (18/50; 27/50; 24/49), and pheochromocytomas in females (1/50; 5/50; 6/50). These tumors were observed at significantly greater incidences (P</=0.05) in the high dose groups than in the vehicle controls. An increased incidence (P=0.028) of hepatocellular adenomas or carcinomas (combined) was observed only in low dose female mice (4/50; 12/49; 4/50). No significant increases in tumor incidences were seen in male mice. Genetic Toxicology: 2-Mercaptobenzothgy: 2-Mercaptobenzothiazole was not mutagenic in Salmonella typhimurium strains TA98, TA100, TA1535, or TA1537 with or without metabolic activation. In the presence of rat liver S9, 2-mercaptobenzothiazole increased the frequency of chromosomal aberrations and sister chromatid exchanges (SCEs) in Chinese hamster ovary (CHO) cells, as well as mutations at the TK locus of mouse L5178Y lymphoma cells. Audit: The data, documents, and pathology materials from the 2-year studies of 2-mercaptobenzothiazole were audited at the NTP Archives. 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 2-mercaptobenzothiazole for male F344/N rats, indicated by increased incidences of mononuclear cell leukemia, pancreatic acinar cell adenomas, adrenal gland pheochromocytomas, and preputial gland adenomas or carcinomas (combined). There was some evidence of carcinogenic activity for female F344/N rats, indicated by increased incidences of adrenal gland pheochromocytomas and pituitary gland adenomas. There was no evidence of carcinogenic activity of 2-mercaptobenzothiazole for maleB6C3F1 mice dosed with 375 or 750 mg/kg. There was equivocal evidence of carcinogenic activity for female B6C3F1 mice, indicated by increased incidences of hepatocellular adenomas or carcinomas (combined). Synonyms and Trade Names: Captax; Dermacid; Mertax; Thiotax; 2(3H)-benzothiazolethione; 2-benzothiazolyl mercaptan

Journal Article↗

NTP Toxicology and Carcinogenesis Studies of Ampicillin Trihydrate (CAS No. 7177-48-2) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

Ampicillin trihydrate is a broad-spectrum semi-synthetic penicillin that is effective in the treatment of gram-positive and gram-negative bacterial infections produced by Streptococcus, Bacillus anthracis, Haemophilus influenzae, Neisseria gonorrhoeae, and Escherichia coli. This antibiotic is used in the treatment of upper respiratory tract infections, genital and urinary tract infections, and otitis media in children. Toxicology and carcinogenesis studies of ampicillin trihydrate (97%-99% pure) were conducted by administering the chemical in corn oil by gavage to groups of 50 F344/N rats and 50 B6C3F1 mice of each sex, 5 days per week for 103 weeks. Male and female rats received doses of 0, 750, or 1,500 mg/kg, and male and female mice received doses of 0, 1,500, or 3,000 mg/kg. Doses selected for the 2-year studies were based on the lack of body weight effects and histopathologic effects at 2,400 mg/kg in the 14-day studies and 3,000 mg/kg in the 13-week studies. Clinical signs in the 13-week studies included diarrhea at 3,000 mg/kg in male and female rats and male mice. Corn oil suspensions containing more than 300 mg ampicillin trihydrate/ml were too viscous to be administered by gavage; therefore, a high dose of 1,500 mg/kg was selected for rats and a high dose of 3,000 mg/kg was selected for mice. During the 2-year studies, mean body weights of male and female rats were similar to or slightly increased over those of the corresponding vehicle control groups. Mean body weights of low dose and high dose male mice were similar to those of the corresponding vehicle group during year 1 of the study but were slightly below those of the vehicle control group during the last half of the study. Mean body weights of low dose and high dose female mice were greater than those of the vehicle controls throughout most of the study. No significant differences in survival were observed in groups of rats or mice of either sex. Clinical signs observed in dosed rats included diarrhea, excessive urination, and chromodacryorrhea and in dosed mice included increased salivation and decreased activity. In male rats, administration of ampicillin trihydrate was associated with an increased incidence of mononuclear cell leukemia (vehicle control, 5/50; low dose, 14/50; high dose, 13/50). Malignant lymphomas were observed in one additional vehicle control male rat and two low dose male rats. Lymphocytic leukemia was seen in one high dose rat. High dose male rats showed increased incidences of pheochromocytomas of the adrenal gland medulla (13/50; 12/50; 23/49). Malignant pheochromocytomas were observed in 1/50 vehicle control, 5/50 low dose, and 1/49 high dose male rats. The incidence of adrenal gland medullary hyperplasia was not increased in male rats (14/50; 10/50; 8/49). There were increased incidences of C-cellhyperplasia of the thyroid gland in low dose male and high dose female rats. High dose male rats showed increased incidences of hyperkeratosis and acanthosis of the forestomach. In male and female mice, ampicillin trihydrate administration was associated with increased incidences of forestomach lesions, including ulcers, inflammation, hyperkeratosis, acanthosis, and evidence of fungal infection. Ampicillin trihydrate was not mutagenic in Salmonella typhimurium strains TA98, TA100, TA1535, or TA1537 in the presence or absence of Aroclor 1254-induced male Syrian hamster or male Sprague-Dawley rat liver S9 when tested according to preincubation protocol. Ampicillin trihydrate was not mutagenic in L5178Y mouse lymphoma cells with or without metabolic activation. Ampicillin trihydrate did not cause chromosomal aberrations or sister-chromatid exchanges in Chinese hamster ovary cells with or without metabolic activation. An audit was conducted for these 2-year studies. Animal/carcass identification discrepancies were observed in rats and mice. The most common findings were the failure to clip some toes in rats and opened ear holes in mice. A review of the inlife data (including body weights, clinical observations, and dosing records) indicrecords) indicated that animals had not been interchanged among groups. The data are considered adequate to support the conclusions. Under the conditions of these 2-year gavage studies, there was equivocal evidence of carcinogenicity of ampicillin trihydrate for male F344/N rats as shown by increased incidences of pheochromocytomas of the adrenal medulla and by marginally increased incidences of mononuclear cell leukemia. There was no evidence of carcinogenicity for female F344/N rats receiving 750 or 1,500 mg/kg or for male and female B6C3F1 mice receiving 1,500 or 3,000 mg/kg per day. Nonneoplastic lesions of the forestomach were seen in male rats and male and female mice. Synonyms and trade names: Acillin; Amcap; Amcill; Aminobenzylpencillin trihydrate; a-Aminobenzylpencillin trihydrate; Amperil; Ampichel; Ampikel; Ampinova; Amplin; Cymbi; Divercillin; Liffampil; Morepen; Pen A; Pensyn; Polycillin; Princillin; Principen; Ro-ampen; Trafarbiot

Journal Article↗

Hyperthermic syndrome in dairy cattle associated with consumption of ergots of Claviceps purpurea in southern Brazil.

A hyperthermic syndrome (HS) associated with consumption of ration contaminated with Claviceps purpurea is described in 4 dairy cattle herds from different counties in the state of Rio Grande do Sul, southern Brazil. Outbreaks of this mycotoxicosis occurred during the summer of 1999-2000 and autumn of 2002 when 25% to 70% of cattle from those herds were affected. The disease occurred after the introduction of a new batch of feed contaminated with sclerotia of C. purpurea. First clinical signs were observed up to 3 mo after the ration was introduced and consisted of pyrexia, intense salivation and drooling, open-mouth, difficult breathing, in some cases with the tongue protruded, decrease in milk yield, decrease in food intake and weight loss. Affected cattle compulsively sought shade or water ponds. Signs were more pronounced during daytime. The severity of the clinical picture varied according to changes in environmental temperature during the day. There was complete recovery approximately 60 d after feeding with the contaminated ration was discontinued. Abortions occurred during the outbreak and soon after the remission of the clinical signs associated with HS. In one of the herds, reproductive performance and fertility were seriously impaired even after clinical signs of HS completely disappeared. Diagnosis was based on epidemiology, clinical signs and pathology. The pathogenetic mechanisms involved in the occurrence of HS are briefly discussed.

Animals↗

[Medical aspects of the lacrimator CS].

Since the 1960's, CS has become the main riot control agent in use by police and army forces throughout the world. The first post-exposure symptom is a burning sensation in the eyes, nose and throat. At a later stage, lacrimation, rhinorrhea, conjunctivitis, sore throat and salivation appear. These symptoms are followed by chest pain and dry cough, and if the substance is swallowed, it may cause nausea and vomiting. This article reviews the physical properties of CS, the main dispersing techniques, the clinical signs and symptoms of exposure, including information on mutagenicity, carcinogenesis, pregnancy safety, and will introduce guidelines for treatment after exposure.

Chest Pain↗

[Toxic pictures produced spiders bites in Chile: latrodectism and loxoscelism].

Latrodectism, produced by the bite of Latrodectus spiders, is worldwide distributed, occurs in hot seasons, and affects mostly men when carrying out agricultural activities. The main symptoms are muscular pain and tremors, profuse perspiration, increased lacrimal, nasal and salival secretions, and hypertension. Symptoms last one week. Neostigmine is a very efficient drug in the treatment of this condition. Loxoscelism, caused by the bite of Loxosceles spiders, is worldwide distributed, affects individuals of all ages. It may present two clinical forms: cutaneous loxoscelism (CL) and viscerocutaneous loxoscelism (VCL). Both forms have been registered in all seasons, with a higher incidence in hot periods, and in bedrooms, when the person is sleeping or dressing. The cutaneous surface of limbs and face are most frequently affected. Local clinical manifestations are pain, edema and livedoid plaque, most of which evolve into a necrotic scar in CL, whereas hematuria, hemoglobinuria, jaundice, fever and sensorial involvement characterize VCL. If visceral involvement does not appear within 24 hours, it is probable that the diagnosis corresponds to CL, with a good prognosis. If a VCL patient survives 48 hours, the possibilities of recovery are high. The patients are successfully treated with parenteral antihistamines or corticosteroids in CL and corticosteroids in VCL.

Adrenal Cortex Hormones↗

Acute poisoning of friesian heifers by Solanum macrocarpon L. ssp dasyphyllum.

Solanum macrocarpon (African eggplant) is a tropical plant widely cultivated as a delicious vegetable; the non-edible wild variety called Solanum macrocarpon L. ssp dasyphyllum (the wild African eggplant) bears thorns or spikes on the stem and leaves. Thirteen yearling heifers on a dairy farm in Uganda suffered acute poisoning after eating berries of S. macrocarpon L. ssp dasyphyllum. There was sudden onset of anorexia, copious salivation, severe dysentery and passage of red urine. The animals also had central nervous derangement (incordination, walking blindly) and exudative dermatitis. Four heifers died. Necropsy lesions were icterus, hemorrhages, gastroenteritis, lympadenomegally, and friable and bronze colored livers and kidneys. The rumen and reticulum contained masses of the plant seeds. This is the first report of cattle poisoning by this plant.

Acute Disease↗

[Sex differences in the cholinergic status of white rats].

Female rats injected with organophosphate inhibitor of acetylcholinesterase chlorophose at doses of 10 mg/kg and 360 mg/kg showed less considerable decrease in blood acetylcholinesterase activity than did male animals. Females compared with males also demonstrated less expressed clinical symptoms of poisoning (salivation, convulsion) after injection of chlorophose at dose of 360 mg/kg. The value of LD50 in female rats was 860 mg/kg, whereas the comparable value in male animals was 700 mg/kg. Following the injection of atropine at doses of 0.1, 0.3, 0.6 mg/100 g female rats showed 2-3 fold increases in basal adrenal and plasma corticosterone levels, but significant decreases in stress-induced corticosterone levels. As for males, the basal and stress-induced values of corticosterone were not significantly affected by atropine administration. These results suggest that functional reserves of cholinergic system and responsiveness of the hypothalamic-pituitary-adrenal axis to cholinergic influence are greater in females than in males. It is concluded that cholinergic status is significantly higher in female rats than in male ones.

Animals↗