Effects of chemical agents on the hepatotoxicity and hepatic accumulation of luteoskyrin

Pretreatment of male mice with 3-methylcholanthrene and promethazine prevented the hepatic accumulation and the hepatotoxicity of luteoskyrin, while piperonyl butoxide and cobaltous chloride had no effect on either. Pretreatment with SKF-525 A elevated SGPT activity in male and female mice. Pretreatment with cycloheximide increased hepatic luteoskyrin accumulation in male mice. Dibenamine prevented hepatic luteoskyrin accumulation and hepatotoxicity only when it was injected in two doses, one the day before and the other concurrently with luteoskyrin. The data suggest that biliary excretion of luteoskyrin may be stimulated by an enzyme other than the microsomal drug metabolizing enzymes. 3-Methylcholanthrene, promethazine and dibenamine may accelerate this excretion thus protecting against luteoskyrin-induced hepatotoxicity. Cycloheximide may prevent this excretory process. The microsomal drug metabolizing enzymes may participate in the detoxification processes of the active form of luteoskyrin.     

A case of hepatocellular carcinoma with multiple lung metastases responding to intermittent intrahepatic arterial chemotherapy of CDDP+5-FU

A 72-year-old man who had multiple hepatocellular carcinoma underwent eight times intrahepatic arterial chemotherapies of SMANCS and two times percutaneous ethanol injection (PEIT) therapies over three years, but new diffuse lesions appeared in the liver. He was treated by intermittent intrahepatic arterial chemotherapy with CDDP 10 mg/body/w and 5-FU 500 mg/body/w. Three months after the start of this therapy, the liver tumor was enlarged and multiple lung metastases appeared. But ten months later, the size of the hepatic lesion was reduced and the lung lesion disappeared. Fifteen months later, a solitary metastatic lesion in the left lung was resected. After two years, peritonitis carcinomatosa was observed, and the patient died.     

EVALUATION OF TISSUE RESPONSE TO PERIODONTAL DRESSINGS: HISTOLOGICAL STUDY IN TOOTH SOCKETS OF RATS

Although the use of periodontal dressings is currently limited, there are some indications for their use. Selection of any material that will have direct contact with live tissues, such as periodontal dressings, should be careful in order to allow surgical wound healing. The aim of this study was to evaluate the intensity of inflammatory response and bone formation in tooth sockets of rats after implantation of three periodontal dressings. After removal of the right maxillary incisors of 84 male rats, each tooth socket received implantation of a polyethylene tube, 63 of which were filled with non-eugenol periodontal dressing and the remaining 21 tubes remained empty (control group). Histological evaluation assessed the intensity of inflammatory response and presence and location of bone tissue formation at postoperative periods of 7, 14 and 28 days. Statistical analysis was performed by the Kruskal-Wallis test at 5% significance level. Regarding the inflammatory infiltrate, at 28 days, there was statistically significant difference between one of periodontal dressings and control group (p<0.05). Analysis of postoperative periods, showed that the control group presented statistically significant reduction in the inflammatory infiltrate comparing the 14- and 28-day periods (p<0.05). Regarding bone tissue formation, there was difference in control group between the 7- and 28-day periods (p<0.05). Within the experimental conditions, it may be concluded that no differences were found in the inflammatory response among the groups at 7 and 14 days and that Voco pac™ dressing induced a more intensive inflammatory reaction at 28 days.     

Occurrence of tooth injuries in patients treated in hospital environment in the region of Araçatuba,Brazil during a 6‐year period

Abstract – Dental trauma has been considered as a public health problem that affects mainly children and youngsters and due to its impact on the patient’s quality of life. This study presents the results of a 6‐year survey of the occurrence and characteristics of dental trauma in patients admitted to the Service of Surgery and Oral and Maxillofacial Traumatology of the School of Dentistry of Araçatuba (UNESP, Brazil) after emergency care in hospital facilities in the region of Araçatuba, SP, Brazil. For such purpose, the clinical files of patients treated at the Service between 1999 and 2005 were reviewed. Information regarding gender, age, number of traumatized teeth, etiology and diagnosis of the trauma was collected from the files of patients with tooth injuries and recorded in case report forms specifically designed for this purpose. The results showed that from a total of 4112 patients admitted to the Service within the surveyed period, 266 (6.5%) had tooth injuries (172 males – 64.7%; 94 females – 35.3%). The total number of traumatized teeth was 496. Most patients belonged to the 16–20 year‐old age group (20.3%) and the most frequent causes of tooth injuries were bicycle accidents (28.6%), motorcycle accidents (19.2%) and falls (18.8%). Injuries to the periodontal tissues were the most frequent type of tooth injuries (408 teeth; 82.26%), occurring in 118 primary and 290 permanent teeth. Among the injuries to the periodontal tissues, avulsion was the most common (32.86%) (29.41% for primary and 34.0% for permanent teeth), followed by extrusive luxation (19.15%) (25.21% for primary and 17.24% for permanent teeth). In conclusion, in the surveyed population, cases of tooth injuries were more frequent in males aged 16–20 years old due to cyclist accidents with predominance of injuries to the periodontal tissues, in particular, avulsions.     

Site-specific phosphorylation of SCG10 in neuronal plasticity: role of Ser73 phosphorylation by N-methyl D-aspartic acid receptor activation in rat hippocampus

Accumulated evidence suggests that actin and microtubule regulating proteins contribute to neuronal structural dynamics, which subsequently affect neuronal plasticity. SCG10 is a neuronal-specific stathmin protein with microtubule destabilizing activity that is affected by multiple phosphorylation, at least in vitro. SCG10 has four major phosphorylation sites: Ser50 and Ser97 targeted by protein kinase A (PKA), and Ser62 and Ser73 targeted by mitogen-activated protein kinase (MAPK). To explore the potential roles of site-specific phosphorylation in physiological models, we developed phosphorylation site-specific antibodies and examined the SCG10 status in primary cultured hippocampal neurons and tissues. Although SCG10 is concentrated in growth cones and the Golgi apparatus in primary cultured neurons, the phosphorylated form was also detected in both regions, suggesting that MT dynamics within the growth cone may be regulated by protein phosphorylation. In the adult hippocampus, an intense stimulus such as kainate treatment induced a rapid phosphorylation of Ser73 within 15 min that was sustained for at least 60 min. This response was mediated through the N-methyl D-aspartic acid (NMDA) receptor and was ablated by the antagonist MK-801. The MAPK enzyme Erk2 was simultaneously activated along a similar time course to SCG10, suggesting that Erk2 may directly phosphorylate Ser73. These results demonstrate that changes in the phosphorylation status of SCG10 in vivo, dependent upon neural activity and/or plasticity, could affect the microtubule dynamics in neuronal dendrites.     

Inositol monophosphatase regulates localization of synaptic components and behavior in the mature nervous system of C. elegans

Although recent studies have provided significant molecular insights into the establishment of neuronal polarity in vitro, evidence is lacking on the corresponding phenomena in vivo, including correct localization of synaptic components and the importance of this process for function of the nervous system as a whole. RIA interneurons act as a pivotal component of the neural circuit for thermotaxis behavior in the nematode Caenorhabditis elegans and provide a suitable model to investigate these issues, having a neurite clearly divided into pre- and post-synaptic regions. In a screen for thermotaxis mutants, we identified the gene ttx-7, which encodes myo-inositol monophosphatase (IMPase), an inositol-producing enzyme regarded as a bipolar disorder-relevant molecule for its lithium sensitivity. Here we show that mutations in ttx-7 cause defects in thermotaxis behavior and localization of synaptic proteins in RIA neurons in vivo. Both behavioral and localization defects in ttx-7 mutants were rescued by expression of IMPase in adults and by inositol application, and the same defects were mimicked by lithium treatment in wild-type animals. These results suggest that IMPase is required in central interneurons of the mature nervous system for correct localization of synaptic components and thus for normal behavior.     

The metabolism of methazolamide - identification of metabolites in guinea pig urine

The in vivo metabolism of methazolamide, a carbonic anhydrase inhibitor, was studied using guinea pigs as the animals. (14)C-Labeled methazolamide was synthesized. Eighty percent of intraperitoneally injected radioactivity was recovered from urine and feces within 24 hours. HPLC analysis on a C(18) column detected 2 radioactive metabolites (Peaks A and B). The Peaks A and B were isolated from the urine of the animals dosed with non-radioactive methazolamide.They were purified on the C(18) column. Their chemical structure was revealed by UV-absorbance spect a and LC/MS, and confirmed by comparing it with that of chemically synthesized compound. They were a glucuronide, (2-acetylimino-3-methyl-Δ(4)-1,3,4-thiadiazol-5-yl)-1-thio-β-D-glucopyranosiduronic acid, and a sulfonic acid, N-[3-methyl-5-sulfo-1,3,4-thiadiazol-2(3H)-ylidene]acetamide.     

Two closely-related left-right asymmetrically expressed genes, lefty-1 and lefty-2: their distinct expression domains, chromosomal linkage and direct neuralizing activity in Xenopus embryos

Background:

Vertebrates have numerous lateral asymmetries in the position of their organs, but the molecular basis for the determination of left–right (L-R) asymmetries remains largely unknown. TGFβ-related genes such as lefty and nodal are L-R asymmetrically expressed in developing mouse embryos, and may be involved in L-R determination.

Results:

We have identified two highly conserved genes, lefty-1 and lefty-2, in the mouse genome. These two genes are tightly linked on mouse chromosome 1. lefty-1 and lefty-2 are both expressed in a L-R asymmetric fashion in mouse embryos. However, the major expression domains of the two genes are different: lefty-1 expression is predominantly confied to the left side of ventral neural tube, whereas lefty-2 is strongly expressed in the lateral plate mesoderm on the left side. In embryos homozygous for the iv and inv mutation, which cause situs inversus, the expression sites of both genes are affected, either reversed or bilaterally, indicating that lefty-1 and lefty-2 are downstream of iv and inv. Although Lefty-1 and Lefty-2 prepro-proteins are not readily processed in cultured cells, BMP2-Lefty chimeric proteins can be processed to a secreted form. We have examined the activities of Lefty-1 and Lefty-2 in Xenopus embryos. In animal cap explants, Lefty-1 and Lefty-2 induce neural cells in the absence of mesoderm induction. The direct neuralizing activities of Lefty-1 and Lefty-2 thus seem remarkably similar to those of BMP antagonists such as noggin and chordin, suggesting that the action of Lefty-1 and Lefty-2 may be to locally antagonize BMP (bone morphogenic protein)-mediated signals in tissues positioned on the left side of the mouse embryos.

Conclusion:

There are two lefty genes in mice (lefty-1 and lefty-2), both of which are expressed in a L-R asymmetric fashion and are downstream of iv and inv. Lefty-1 and Lefty-2 possess direct neuralizing activity in Xenopus embryos, resembling the activities of BMP antagonists.