NaF activates MAPKs and induces apoptosis in odontoblast-like cells.

The cytotoxic effects of fluoride on odontoblasts are not clear. In this study, we examined whether NaF induces apoptosis in MDPC-23 odontoblast-like cells and the involvement of mitogen-activated protein kinase (MAPK) signaling pathways in NaF-induced apoptosis. MDPC-23 cells incubated with 5 mM NaF for 24 hrs exhibited caspase-3 activation, cleavage of poly(ADP-ribose) polymerase, DNA fragmentation, and an increase in cytoplasmic nucleosomes. Prior to the induction of apoptosis, all MAPKs examined were phosphorylated, but in a different manner. In contrast to the sustained phosphorylation of c-Jun NH(2)-terminal kinase (JNK) and p38, NaF exposure induced a biphasic phosphorylation of extracellular signal-regulated protein kinase (ERK). NaF-induced apoptosis was markedly suppressed by treatment with the JNK inhibitor, SP600125, and mildly suppressed by the MAPK/ERK kinase inhibitor, U0126. Inhibition of p38 activity did not protect cells from apoptosis. Thus, exposure to NaF induces apoptosis in odontoblast-like cells, depending on JNK and, less significantly, ERK pathways.

Fatty liver suppressed the angiogenesis in liver metastatic lesions.

BACKGROUND/AIMS: We have demonstrated that colorectal cancer with fatty liver had few liver metastases clinically as well as experimentally. In this study, to clarify why colorectal cancer with fatty liver had few liver metastases, we focused on the angiogenesis of carcinomas. METHODOLOGY: The rat colon cancer cells (RCN-9) were injected into 40 rats (the fatty liver group = FL group includes 20 rats, the non-fatty liver group = NFL group includes 20 rats). In each group, the PyNPase (pyrimidine nucleoside phosphorylase) activity in the metastatic lesion of the liver was examined using the high-performance liquid chromatographic method. In addition, the microvessel density in the metastatic lesion of the liver was assessed by Von Willebrand factor-related antigen immunostaining. RESULTS: 1) The PyNPase activity in the FL group was 33.34 +/- 6.27 (microgram FU/mg protein/hr), which was significantly lower than that of the NFL group (49.30 +/- 14.82) (P = 0.0021). 2) Microvessel density in the FL group was 1.845 +/- 0.357 (%), while that in the NFL group was 2.777 +/- 1.371 (%). The microvessel density of the FL group was significantly lower than that of the NFL group (P = 0.0365). 3) The regression coefficient between PyNPase activity and microvessel density was 0.480, which indicated a significant correlation (P = 0.0098). CONCLUSIONS: We think that, in colorectal carcinomas with fatty liver, the decreased activity of PyNPase and the decreased neovascularization in the metastatic lesion are closely related to fewer liver metastasis compared with colorectal cancer patients without fatty liver.

In vitro toxicity of gallium arsenide in alveolar macrophages evaluated by magnetometry, cytochemistry and morphology.

Gallium arsenide (GaAs), a chemical compound of gallium and arsenic, causes various toxic effects including pulmonary diseases in animals. Since the toxicity is not completely investigated, GaAs has been used in workplaces as the material of various semiconductor products. The present study was conducted to clarify the toxicity of GaAs particles in the alveolar macrophages of hamsters using magnetometry, enzyme release assays and morphological examinations. Alveolar macrophages obtained from hamsters by tracheobronchial lavage and adhered to the disks in the bottom of wells were exposed to ferrosoferric oxide and GaAs particles. Ferrosoferric oxide particles were magnetized externally and the remanent magnetic field was measured. Relaxation, a fast decline of the remanent magnetic fields radiated from the alveolar macrophages, was delayed and decay constants were decreased dose-dependently due to exposure to GaAs. Because the relaxation is thought to be associated with cytoskeleton, the exposure of GaAs may have impaired the motor function of them. Enzyme release assay and morphological findings indicated the damage to the macrophages. Thus the cytotoxicity causes cytostructural changes and cell death. According to DNA electrophoresis and the TUNEL method, necrotic changes occur more frequently than apoptotic changes.

Adverse effects of colophony.

Regarding colophony, the use in industries, adverse effects, diagnosis, pathophysiology and control are reviewed. Colophony is an unhomogeneous mixture of resin acids as like abietic acid and neutral substances. Colophony is used everywhere, in industry, daily life and medical supplies. Soldering workers are exposed to the colophony fumes heated up to the temperature of soldering irons. The effects of exposure to colophony are classified into bronchial asthma and contact dermatitis. Colophony fumes cause bronchial asthma by its nonspecific irritation. Inhalation challenge test and repeated spirometry during working day may help the diagnosis of colophony induced asthma. Improvement of working environment for soldering and development of new flux instead of colophony will be necessary. A study on contact dermatitis revealed that colophony and its related compounds are one of major causes for contact dermatitis. Cases of dermatitis by depilatory agents used to remove hair from slaughtered swine, anti-slipping cream for ballet shoes or resin for cello strings have been reported. Patch test may contribute to the diagnosis of dermatitis caused by colophony.

Concentration in blood and organs of dogs after high dose 1,1,1-trichloroethane inhalation.

Dogs were exposed to 1% (v/v) (10,000 ppm) vapor of 1,1,1-Trichloroethane (1,1,1-TCE) by inhalation for 3 min repeated four times at 4 hr intervals under continuous anesthesia. Changes in the 1,1,1-TCE concentration in blood with time, as well as distribution of 1,1,1-TCE in the organs and tissues (lungs, liver, kidneys, heart, brain, and fat around the kidneys and on the abdominal wall) upon completion of the four exposures were studied. Concentrations of 1,1,1-TCE in blood showed the highest level immediately after exposure, and fairly decreased in about 30 min after exposure. The half life of 1,1,1-TCE in blood was 4-12 min after exposure. Upon completion of the exposures (3 min inhalations repeated four times), 1,1,1-TCE concentrations per gram wet weight of each organ ranged from 0.1 to 0.5 microgram/g in the lungs, liver, kidneys, heart and brain. On the other hand, the 1,1,1-TCE concentration in fat ranged from 16.9 to 54.6 micrograms/g, greatly exceeding those in other organs.

Benefit of in vitro fertilization treatment for endometriosis-associated infertility.

OBJECTIVE: To evaluate the effectiveness of IVF treatment in endometriosis-associated infertility. DESIGN: Nonrandom retrospective study. SETTING: Department of Gynecology and Obstetrics, Akita University School of Medicine. MAIN OUTCOME MEASURE(S): Cumulative pregnancy rate. PATIENT(S): One hundred eighteen infertile patients in whom diagnosis of endometriosis was established by laparoscopic examination. INTERVENTION(S): The prognoses of 60 patients (IVF group) who started IVF treatment within 6 months after laparoscopy were compared with those of 58 patients who were managed expectantly without IVF treatment during the same period. RESULT(S): The cumulative conception rates at 36 months after laparoscopy were 62% in the IVF group and 43% in the control group, and the difference was not significant (a log-rank test). For patients > or = 32 years of age, the conception rates were significantly higher in the IVF group (59% versus 29%). A relatively large but nonsignificant difference in the conception rate between the two groups was observed in patients with endometriosis at stages III or IV (52% versus 27%). CONCLUSION(S): In vitro fertilization treatment provides better prognosis in patients > or = 32 years of age and is recommended for such patients. The benefits of treatment appear to be greater in patients with more advanced stages of endometriosis.

Status of the coagulation and fibrinolytic systems in ovarian hyperstimulation syndrome.

OBJECTIVE: To elucidate characteristic changes of plasma hemostatic markers in ovarian hyperstimulation syndrome (OHSS) cycles. DESIGN: Prospective study. SETTING: The IVF-ET program of the Department of Obstetrics and Gynecology, The University of Akita, School of Medicine. PATIENTS: Forty cycles of 40 IVF patients, including 12 cycles in which a severe form of OHSS occurred. INTERVENTIONS: Blood samples were taken during IVF treatment to determine the levels of blood markers that reflect activation of the coagulation and fibrinolytic systems. MAIN OUTCOME MEASURES: Thrombin-antithrombin III complexes, plasmin-alpha 2 antiplasmin complexes, and other hemostatic markers related to the coagulation and fibrinolytic system activation. RESULTS: In the OHSS cycles, the levels of thrombin-antithrombin III and plasmin-alpha 2 antiplasmin complexes in the plasma began to rise within a few days after hCG administration and demonstrated significantly higher levels during the midluteal phase. In OHSS cycles with pregnancy, elevation of these markers continued for > or = 3 weeks after the onset of disease. There were some characteristic changes in OHSS cycles in other hemostatic markers, such as a decrease in the levels of antithrombin III and prekallikrein and shortened activated partial thromboplastin time. CONCLUSION: These data demonstrate the status of the coagulation and fibrinolytic systems in OHSS cycles and provide insight into the mechanism of activation in the hemostatic system.

In vitro fertilization of in vitro matured oocytes obtained from the follicles without hCG exposure for prevention of severe ovarian hyperstimulation syndrome: a case report.

We aspirated ovarian follicles of an infertile patient who encountered a great risk of ovarian hyperstimulation (OHSS) during her ovulation-induction cycle, which had been stimulated with gonadotropins, in order to avoid OHSS without interrupting the treatment. If this action were to yield a considerable number of immature oocytes, some of which were to achieve in vitro maturation and subsequent fertilization, this method could be an alternative to conventional ovulation-induction methods for patients who repeatedly present imminent signs of hyperstimulation. However, the number of oocytes collected from the patient was disappointingly low, even though a large number of follicles were thoroughly aspirated. One of these oocytes was matured in vitro in a medium containing 30% follicular fluid and granulosa cells of mature follicles, fertilized, cryopreserved, and transferred in a later artificial cycle; but pregnancy was not achieved. A low number of recovered oocytes from patients in this situation might be a factor that greatly limits the clinical applications of this method.

Characteristics of blood hemostatic markers in a patient with ovarian hyperstimulation syndrome who actually developed thromboembolism.

OBJECTIVE: To investigate whether a patient with ovarian hyperstimulation syndrome (OHSS) demonstrated characteristic changes in the blood hemostatic markers before she developed thromboembolism. DESIGN: Patients with OHSS had blood drawn to determine hemostatic markers and related factors. PATIENTS: Twenty-three OHSS patients, including a case complicated with thromboembolism. SETTING: The IVF-ET program of the Department of Obstetrics and Gynecology, The University of Akita, School of Medicine. MAIN OUTCOME MEASURES: Blood hemostatic markers and related factors. RESULTS: The patient with thromboembolism demonstrated marked leukocytosis and higher levels of activation in the blood markers related to fibrinolytic system, such as alpha 2 plasmin inhibitor, plasmin-alpha 2 antiplasmin complexes, and D-dimers, before the onset of this episode. CONCLUSION: Marked leukocytosis and higher levels of activation of the fibrinolytic system may be the signs of imminent thromboembolism in OHSS patients.

Prospective evaluation of simple morphological criteria for embryo selection in double embryo transfer cycles.

Preventing the occurrence of high-rank multiple pregnancies without reducing the pregnancy rate remains a high priority of in-vitro fertilization and embryo transfer programmes. Our previous study demonstrated that, if there is at least one embryo with a good morphological grade, then the transfer of two (a double embryo transfer) instead of three embryos does not result in a lower pregnancy rate, and that the influence of the number of embryos transferred becomes significant only when poor-quality embryos are transferred. This result allowed us to employ the simple policy of systematically selecting double embryo transfer cycles without affecting the pregnancy rate. Since January 1994, when patients < 37 years of age had more than two embryos available for transfer, only two instead of three embryos were transferred if at least one of the embryos demonstrated a good morphological grade. After a 1 year application of this policy, of the 147 cycles (group A) that fulfilled the above criteria, two embryos were transferred in 92 cycles, while three embryos were transferred in the other 55 cycles. The results of these cycles were compared to those of the control 144 cycles (group B) in which three embryos were transferred, prior to the application of this policy. The on-going pregnancy rates and the incidence of multiple and triplet pregnancies were 24% and 28%, 22% and 23%, and 2% and 9% in groups A and B respectively. The rates were not significantly different. In conclusion, although our prospective trial demonstrated a tendency of decreasing pregnancy rate and an invariable incidence of multiple pregnancies, the very low occurrence of triplets during this period indicated that this policy provided a practical compromise between achieving a high pregnancy rate and an acceptable incidence of triplet pregnancies.

High incidence of embryo transfer cancellations in patients with polycystic ovarian syndrome.

This study was aimed at assessing the outcome of in-vitro fertilization (IVF) and embryo transfer in patients with polycystic ovarian syndrome (PCOS). The results of IVF and embryo transfer in PCOS patients (PCOS group, 78 cycles of 26 patients) were compared with those of a control group (423 cycles in 202 patients without male factor; age and ovarian stimulation protocol were matched). Although the pregnancy rate per transfer was not different in the two groups of patients (25 versus 34%, PCOS versus control group), the PCOS group had a significantly lower pregnancy rate per follicle aspiration (19 versus 31%, P < 0.05). A notable result was a significantly higher incidence of embryo transfer cancellations in the PCOS group (22 versus 8%, P < 0.01), which resulted from unpredictable failure of either oocyte recovery or fertilization. The incidence of unexplained complete failure of fertilization was significantly higher in the PCOS group (18 versus 5%, P < 0.01). These results may reflect a reduced quality of the oocytes in the PCOS group, and there was a subgroup of PCOS patients who repeatedly produced poor results of treatment. Although the ovarian stimulation regimen best suited to PCOS patients remains to be determined, special care should be taken during ovarian stimulation, especially when the PCOS patients had experienced unexplained failure of oocyte recovery or fertilization in the previous treatment cycle(s).

[Oil mist exposure in industrial health--a review].

Many reports dealing with the toxicity of oil mist in industrial health have been published. The condition appears to be worldwide in distribution and the number of reported cases increases with increasing clinical awareness. In 158 reports published from 1965 to 1993 the following diseases were observed: Skin--contact dermatitis, oil acne and photosensitive allergic dermatitis; Scrotum--benign and malignant tumors; Respiratory system-nasal discomfort symptoms, rhinitis, nasal mucosal dysplasia, nasal mucosal tumor, laryngeal cancer, bronchitis, lipoid pneumonia, lung fibrosis, lung cancer and bronchial asthma; Others--possible carcinogenicity, high incidence of chromosomal change. This shows that oil mist appears to be involved in many industrial diseases, however, cause-and-effect relationship still remains a matter of conjecture; in which exposure dose and/or duration-dependent toxicity is highly probable. Further investigations will be required including immunotoxicological as well as environmental studies for oil mist exposure.

[A study on the mechanism of thrombosis in ovarian hyperstimulation syndrome (OHSS)].

The purpose of this study was to investigate whether endothelial cell procoagulant activity (PCA), which triggers the extrinsic coagulation pathway, is involved in thrombosis in patients with ovarian hyperstimulation syndrome (OHSS). PCA in OHSS sera was measured by an activation of tissue factor expression on cultured human umbilical vein endothelial cells (HUVEC). The substance responsible for the expression of PCA in sera was partially purified and characterized. The results obtained were as follows. (1) OHSS sera contained significantly (p < 0.05) higher PCA than in controlled women (during the follicular phase). Fetal cord sera contained very strong PCA. (2) There was no correlation between PCA and the level of either estradiol (E2) or progesterone (P4) in OHSS sera. (3) The substance that expresses PCA in fetal cord sera was heat-labile with high affinity for heparin sulfate and had a molecular weight of approximately 100,000. These results support these conclusion: (1) PCA is involved in thrombosis in patients with OHSS and (2) neither the serum level of E2 nor that of P4 is associated with PCA.

[Changes of microsomal cytochrome P-450 content in carbon tetrachloride-induced acute liver damage in mice--comparison to the extent of histopathological changes].

Changes in the levels of hepatic microsomal P-450 were measured in mice during the course of acute liver injury induced by carbon tetrachloride (CCl4), and the findings were compared to the extent of histopathological changes. Seventy-two male mice were divided into three groups: Group (I), no treatment, used for liver P-450 assay; Group (II), treated with CCl4 plus an equal amount of olive oil at a dose of 0.2 ml/100g body weight; and Group (III), received olive oil alone. Predominant hepatic changes observed in the mice of group II were centrilobular hemorrhage with necrosis occurred by 24 hours after CCl4 administration. Microsomal cytochrome P-450 level decreased up to 25% of that control. In contrast, no appreciable change was seen either histopathologically or biochemically in the mice of group III. The observed decrease in liver microsomal cytochrome P-450 content suggested the possibility that detoxification capacity of endoplasmic reticulum in CCl4-injured hepatocyte was highly impaired and the impairment affected the following various functions of the tissues in animals.

Magnetometric evaluation of the effects of gallium arsenide on the clearance and relaxation of iron particles.

Intratracheal instillation of GaAs suspension has been histopathologically shown to induce a diffuse pulmonary response. In the present study, magnetometry was used to evaluate the effects of intratracheally instilled GaAs on the behavior of externally magnetized iron particles instilled in rabbit lung. Magnetometric evaluation of the effects of GaAs in rabbits dosed with 30 mg or 300 mg/animal showed significant decreased relaxation of iron particles at 1, 3, 7, 14, 21 and 28 days following instillation compared with the controls. Relaxation indicates a rapid decrease of remanent magnetic field following magnetization of the lungs due to random rotation of phagocytized iron particles in macrophages. Clearance of the iron particles was measured by serial determinations of the remanent magnetic field at the end of magnetization estimated from relaxation curves. Clearance was significantly impaired in rabbits exposed to both doses of GaAs at 14, 21 and 28 days after instillation. Dose-effect relationships were observed in both cases. Histological examination of lungs instilled with these doses indicated active phagocytosis of GaAs and iron particles by alveolar macrophages.