Organoleptic excipients used in pediatric antibiotics.

Taste is a crucial factor that determines the palatability of the oral dosage form and patient compliance. OBJECTIVE: The aim of this work was to evaluate the organoleptic excipients in oral antibiotics for pediatric use marketed in Brazil. METHODS: The information was obtained from the GuidetoPharmacy, a reference for the pharmaceutical trade. The analysis included dosage forms for oral administration and drugs and their combination with antibacterial action. After this survey, we identified the constitution of the flavoring, sweetening, and coloring agents of each medicine. The results are presented in a descriptive form. RESULTS: Twelve drugs or associations are distributed in 70medicines. Oral suspension was the most common pharmaceutical dosage form. Sweeteners were sucrose, sodium saccharin, and sodium cyclamate. All the coloring agents observed are synthetic and the most frequent ones were yellow twilight no. 6, yellow tartrazine no. 5, and red ponceau 4R. The presence of two or more types of flavorings per medicine was observed. CONCLUSION: Antibacterials use coloring agents, flavorings, and sweeteners to facilitate the administration of medicines for children, using up to six different substances per formulation. No natural coloring agent was observed, demonstrating an issue to be explored in the future. It is important to note that, although necessary, these excipients are responsible for a high incidence of allergic reactions in children.

Interleukin-6-induced activation of signal transducer and activator of transcription-3 in ruptured rotator cuff tendon.

The aim of this study was to examine interleukin-6 production and the activation of signal transducer and activator of transcription-3 (STAT3) in ruptured rotator cuff tendon. Specimens of ruptured rotator cuff tendons were analysed using real-time reverse transcriptase polymerase chain reaction, Western blotting and immunohistochemistry. Specimens of co-existing inflammatory subacromial synovia were examined for comparison. The level of interleukin-6 messenger RNA was increased in ruptured rotator cuff tendon as well as in subacromial synovium. Western blot analysis showed constitutive production of activated, phosphorylated STAT3 in ruptured rotator cuff tendon and co-existing subacromial synovium. Immunohistochemical examination detected cells producing interleukin-6, interleukin-6 receptor and phosphorylated STAT3 in ruptured rotator cuff tendon, mainly in proliferative vessels and, to a lesser extent, in tendon fibroblasts around the vessels. This study demonstrates that activation of STAT3 induced by interleukin-6 is promoted mainly by proliferative vessels in ruptured rotator cuff tendon.

Effects of simvastatin on serum lipids and atherosclerosis in WHHL rabbits.

Watanabe heritable hyperlipidemic rabbits aged three months (young group) or 10 months (adult group) received 10 mg/kg of simvastatin daily for 24 weeks. Serum levels of total cholesterol, triglycerides, and beta-lipoproteins were reduced significantly in the treated animals but not in untreated controls. The decreases were greater in the young than in the adult animals. Levels of high-density lipoprotein cholesterol were not affected by treatment. At 24 weeks, the extent of atheromatous lesions on the thoracic-abdominal aorta was lower in the treated animals than in the controls, but the difference was significant only in the young animals. The results indicate that simvastatin would be effective in the treatment of atherosclerosis.

Herpes simplex virus bronchopneumonia in a non-immunocompromized individual.

We report a rare case of herpes simplex virus (HSV) bronchopneumonia in an otherwise healthy middle-aged individual. Bronchoscopy indicated scattered white-coated lesions in the bronchial mucosa. The diagnosis was established following immunohistopathological staining for HSV of specimens obtained by bronchial biopsy. This case suggests that HSV could be a pathological agent of not only oral and genital mucosal lesions but also lower respiratory tract infection.

[Single and 4-week oral toxicity studies of prulifloxacin (NM441) in aged dogs].

Single-dose and repeated dose toxicity studies of prulifloxacin, a new antibacterial agent, were conducted in aged beagle dogs. I. A single-dose toxicity study Prulifloxacin was administered orally to aged female dogs at a single dose of 2500 and 5000 mg/kg. No death occurred in any group. Vomiting was observed in one of two animals at 2500 mg/kg and in both animals at 5000 mg/kg 3-4 hr after dosing. At 5000 mg/kg, vomiting was observed in both animals after feeding on the day after dosing. One animal also showed soft stool. Thereafter, no abnormalities were observed in any animal. No test article related changes were noted in food consumption, water consumption, body weight or pathological examination in any group. The results show that the lethal dose of prulifloxacin is judged to be greater than 5000 mg/kg in aged female dogs. II. A repeated dose toxicity study Aged male and female dogs were given the test article orally for 4 weeks at doses of 0 (control), 20, 100 and 500 mg/kg. No death occurred in any group. At 500 mg/kg, vomiting was observed every day or intermittently throughout the dosing period and salivation was observed almost every day from day 6 to the end of the dosing onward. Decreases or lack of food and water consumption, and decrease of body weight were noted at 500 mg/kg. At 100 mg/kg, slight decreases in food consumption and body weight were noted in the females. No abnormalities were noted in ophthalmoscopic or electrocardio-graphic examination. In urinalysis, decreases in Na+, K+ and Cl- concentrations and the total excretion amount were noted mostly at 500 mg/kg. A low specific gravity was noted in males at 500 mg/kg. In hematology and serum biochemistry, high GPT, BUN and creatinine, and decreases in WBC were noted in both sexes at 500 mg/kg. A high GOT was noted in males, and low Cl- in females at 500 mg/kg. At 100 mg/kg, a high GPT was noted. Rough surface in the kidney and chronic interstitial nephritis (basophilic change of tubule, atrophy of tubule, thickening of tubular basement membrane, interstitial mononuclear cell infiltration, interstitial focal fibrosis) were increased at 500 mg/kg. No toxicological findings were seen in the 20 mg/kg group. The results show that the NOAEL of prulifloxacin is 20 mg/kg for 4-week repeated dose toxicity in aged dogs.

Locus of dominant hairless gene (Ht) causing abnormal hair and keratinization maps to rat chromosome 10.

The rat dominant hairless gene (Ht) of the WBN/Ila-Ht rat causes atrichosis in Ht/Ht and hypotrichosis in Ht/+. Furthermore the Ht/Ht shows signs of abnormal keratinization and almost all of the Ht/Ht die in an immature stage before weaning in the conventional environment. Ht/+ was affected by dermatitis caused by Staphylococcus aureus, suggesting that the gene Ht might involve defense mechanisms against infection. In this study, we performed the linkage analysis of the gene Ht by outcross with the Brown Norway rat in the SPF environment. Ninety-six backcross progeny of (BN x WBN/Ila-Ht/Ht) F1 x WBN/Ila-Ht/Ht were typed with microsatellite markers and the gene Ht was mapped on chromosome 10 between Asgr1 and Nos2 within the map distance of 6.2 cM.

Deodorization of laboratory animal facilities by ozone.

Deodorizing effect of ozone was investigated comparing two types of compact ozonizing apparatus made on an experimental basis. The concentrations of ammonia and trimethylamine were examined as an indicator for deodorizing effect of ozone in animal rooms of rats and guinea pigs at laboratory animal facilities of three different universities. Both of the ozonizing apparatus were able to remove ammonia and trimethylamine in animal rooms, with no significant difference in the performance of the two apparatus.

[Clinical study on mechanism of Pneumocystis carinii pneumonia by polymerase chain reaction].

Pneumocystis carinii is a human respiratory pathogen which causes fatal pneumonia in patients under immunosuppressed or immune deficient conditions. Recent work have documented the usefulness of the polymerase chain reaction (PCR) method in the detection of P. carinii from clinical samples. Therefore, we described our experience in using PCR method in the detection of P. carinii from respiratory samples. In our study, bronchial washing or BALF were good for diagnosis of P. carinii pneumonia (PCP) by PCR. However, PCR method in the detection of P. carinii from swab or sputum was too sensitive because small numbers of P. carinii organisms might be insignificant in causing the disease. It might reveal colonization or asymptomatic carrier state in the upper respiratory tract. Therefore, our result suggested that colonization or asymptomatic carrier state in the upper respiratory tract could eventually evolve into PCP. This would also facilitate basic progress in the pathology or epidemiology of P. carinii infection. In addition, an usefulness of prophylactic therapy for PCP was documented by PCR.

[A case of ankylosing spondylitis associated with pulmonary aspergillosis and amyloidosis].

A 56-year-old man was admitted because of diarrhea, cough, weight loss, and disturbance of consciousness. He had been diagnosed as having ankylosing spondylitis at 18-years old. The spondylitis progressed until there was complete rigidity of the spine including the neck, hip and knee joints. Human leukocyte antigen (HLA) B27, which has been characteristic of ankylosing spondylitis, was also present in this case. A chest radiograph showed pleural thickness and a cavity in the right upper lobe; and a soft tissue mass and fluid level was found in the cavity. Aspergillus fumigatus was detected in the sputum and pulmonary aspergillosis was diagnosed. Biopsy of the colon revealed that a large interstitial amyloidosis. Despite the treatment of the patient's malnutrition and lung aspergillosis using amphotericin B, the clinical course was rapidly progressive and the patient died of respiratory failure due to lung aspergillosis. It is important to be aware of these rare complications, which are correlated with the prognosis in cases of ankylosing spondylitis.

[Pharmacokinetic studies of menogaril (TUT-7) with rats].

Menogaril (TUT-7) is a novel antitumor antibiotic belonging to anthracyclines. The pharmacokinetic parameters derived from plasma concentration-time profiles after repeated (for 14 days) or single oral administration of TUT-7 to rats were found to be not significantly different by either administration schedule. The rats with artificial liver dysfunction were obtained by subcutaneous application of carbon tetrachloride (CCl4, 1 ml/kg) for 3 days. After oral administration of TUT-7 to the rats with CCl4-induced liver toxicity (3 daily administrations of 1mg/kg, S.C.), the maximum plasma concentrations (Cmax) and AUC of both the unchanged drug and its metabolite N-Demethyl menogaril, were increased. Also over all elimination was slower in animals with liver dysfunction.

Studies on diabetic syndrome and influences of long-term tolbutamide administration in Mongolian gerbils (Meriones unguiculatus).

Sixty-seven mongolian gerbils (Meriones unguiculatus), which seem to resemble the sand rats in the manifestation of diabetic syndrome, were used for observations on the development of diabetic process and on the effect of the long term administration of tolbutamide on it. The mean blood glucose (158.2 +/- 14.7 mg/100 ml), mean serum NEFA (0.70 +/- 0.34 mEq/l) and mean serum IRI (68.9 +/- 10.2 muU/ml) in mongolian gerbils were relatively higher than those in rats. Diabetes-like processes found in the pancreas of mongolian gerbils were roughly grouped into two main types: (1) the histopathological process in which the fibrosis, initially prominent at perivascular space, spread to the islets, finally producing the islet's cell degeneration, and (2) the process of diffuse islet's hyperplasia. These two processes were considered to differ from each other, the former being affected by tolbutamide and the latter remaining unaffected. After breeding on the diet containing 0.1 -0.2% tolbutamide for 6 months, there was a general inclination of an increase of cases of severe pathological findings, and the distribution probabilities of the cases carrying the severe fibrotic process in heart, that is, the process from endothelial cell swelling, medial fibrosis and obliterative changes in cardiac arteries which was resulting in the focal degeneration of cardiac muscle, was significantly higher than in the non-treated group. It was concluded that mongolian gerbil might be recommended as a model of experimental diabetes and that tolbutamide seemed to have some harmful effects on the diabetes-like process in mongolian gerbils.

Hysteroscopic appearance of the mid-secretory endometrium: relationship to early phase pregnancy outcome after implantation.

A total of 172 patients who underwent hysteroscopic assessment of the endometrium and then became pregnant, was analysed retrospectively to explore the relationship between endoscopic findings and early phase pregnancy outcome after implantation. Histological examination of the endometrium and assay of serum progesterone and oestrogen were carried out simultaneously with hysteroscopy. Of 172 patients, 12 were excluded. Of the remaining 160 patients, 62 (38.8%) were classified endoscopically as having 'good' mid-secretory endometrium and 98 (61.3%) as 'poor', between one and four cycles prior to the conception cycle. There were no clinical differences between these two groups, except that the frequency of patients with a history of early abortion was significantly higher in the 'poor' group (25.5%) than in the 'good' group (8.1%) (P < 0.05). Of 160 pregnancies, 118 persisted successfully to live birth, but 42 ended in early pregnancy loss. The incidence of early abortion was significantly higher in the 'poor' group (33.7%) than in the 'good' group (14.5%) (P < 0.05). Significant differences were observed between the two groups for histological dating of the endometrium (P < 0.05) but not for serum progesterone and oestradiol concentrations or progesterone:oestradiol ratio. In conclusion, our data suggest that the hysteroscopic appearance of the mid-secretory endometrium at this stage of the menstrual cycle is a better prognostic factor for pregnancy outcome than hormonal data.

Immunophenotyping of lymphocytes in the lung interstitium and expression of osteopontin and interleukin-2 mRNAs in two different murine models of pulmonary fibrosis.

In the surfactant protein C/tumor necrosis factor (SP-C/TNF) transgenic mouse, the TNF-alpha transgene is overexpressed in type II pneumocytes. Pulmonary lymphocytic infiltration develops which is followed by fibrotic changes including accumulation of fibroblasts and deposition of extracellular matrix. We hypothesized that lymphocytes played a role in the development of pulmonary fibrosis in this model. Lymphocytes were recovered from the interstitium of the lung and analyzed by flow cytometry. The absolute number of lymphocytes recovered from transgenic mice were approximately four times of that in littermates. Flow cytometric analysis showed the presence of gamma delta T cells and B1 cells in the former group but these cells were almost absent in the lung of non-transgenic littermates. We also studied lymphocytes accumulating in the lung during bleomycin (BLM)-induced pneumopathy. Serial analyses showed a progressive increase of CD4/CD8 ratio after injection of BLM, reaching a peak at day 14, then decreased to the normal level by day 48. Northern blot analysis of the lung showed an enhanced expression of interleukin (IL)-2 and osteopontin (OPN) mRNA in those two models of pulmonary fibrosis. Expansion of clonal alpha beta T cells as detected by reverse transcriptase-polymerase chain reaction/single strand conformation polymorphism (RT-PCR/SSCP) suggests involvement of antigen-driven mechanisms in the development of pulmonary fibrosis.

Spontaneous diabetes-like syndrome in WBN/KOB rats.

Spontaneous hyperglycemia, glycosuria, hypoinsulinemia, and glucose intolerance were observed in some WBN/Kob rats, at about 9 months of age, and in all at the age of 17 months. Females did not present this pathology. Histopathologic examination of the pancreas revealed severe changes in male rats at the age of 3 months. Between 3 and 6 months of age a distinct infiltration of inflammatory cells was found around islets and among adjacent acinar cells. At the same time, marked fibrosis was seen around the pancreatic ducts and blood vessels. With advancing age the fibrous tissue gradually invaded extensive areas of the pancreas where also the islets became involved in fibrotic degeneration. At 17 months of age and later, an obvious decrease in islet number and size (less than 50 mu in diameter) was observed, even in relatively unaffected areas of the organ. Frequent bilateral cataracts began to appear at about 15 months of age. Opacities were first observed in the periphery of the lens, then increased rapidly in intensity and extended centripetally. Nineteen-month-old male rats were hypersensitive to exogenous insulin, but showed no significant decrease in blood glucose level when treated with oral tolbutamide. These results suggest that these rats suffered from a decreased insulinogenic response.

Renal lesions in a strain of spontaneously diabetic WBN/Kob rats.

In WBN/Kob strain rats, only males spontaneously develop hyperglycemia, glycosuria, hypoinsulinemia and glucose intolerance from about nine months of age. The kidneys of male rats of this strain were histopathologically studied to evaluate the changes which appeared as complications of diabetes mellitus. Thickening of the basement membrane, increase of the mesangial matrix and fibrin-cap lesions were noted in the glomeruli. Armanni-Ebstein degeneration was occasionally found in the tubules. Linear deposition of plasma components such as IgG and albumin in the basement membrane of the glomeruli, tubules and Bowman's capsule characterized the immunohistological pattern. These findings are similar to the findings in diabetic nephropathy in humans. Since the onset of diabetes mellitus in the strain is slow and symptoms are generally mild, insulin administration is usually not necessary for survival. This strain, therefore, appears to be an important animal model for the study of complications of diabetes in humans.