Photodynamic Therapy of Malignant Gliomas.

Recently, the clinical applications of photodynamic therapy (PDT) in the management of malignant brain tumors have attracted significant attention. Meta-analysis of the observational studies on this treatment in high-grade gliomas (Eljamel, 2010) included more than 1,000 patients and reported median survival in cases of newly diagnosed and recurrent glioblastoma multiforme (GBM) of 16.1 and 10.3 months, respectively. In some series, increase in the long-term survival rates was also observed. Few controlled trials demonstrated statistically significant impact of PDT on prolongation of survival in patients with GBM in comparison to conventional management. The main treatment-related adverse event is short-lasting excessive photosensitivity of the skin and retina after photosensitizer administration, but its negative consequences can be easily avoided with appropriate protective measures. Overall, PDT may be considered to be a safe and effective adjuvant therapeutic option for patients with newly diagnosed and recurrent malignant gliomas. Aggressive tumor resection seems to be an important prerequisite to maximize treatment efficacy.

Whether to excise a lipofibroma of the median nerve.

A 28-year-old man presented with a lipofibroma of the median nerve of the left hand. We released the carpal tunnel, did a neurolysis, and biopsied of the median nerve together with a distal fasciotomy of the forearm. Two years after the operation, the paraesthesiae of the middle finger had improved but was still present to a lesser degree. Initial considerations about treatment should be directed toward biopsy and alleviation of the compression neuropathy, rather than total excision.

Solitary periosteal chondroma presenting as a snapping finger: an unusual location.

We report an unusual case of a solitary periosteal chondroma presenting as a snapping finger and pain in the ring finger in a 37-year-old man. The snapping symptom was caused by impingement of this solitary chondroma. In this case, the periosteal chondroma was detached due to a finger sprain. Thus, the solitary chondroma was impinged between basal phalanx and extensor tendon, causing the pain and snapping finger. When patients with snapping finger present, CT scans can be helpful to make a correct diagnosis. To the best of our knowledge, this condition has not been described in the PIP joint.

Flexor digitorum profundus avulsion of the left little finger through enchondroma of the distal phalanx: pull-out wire technique treatment without bone graft.

This case report describes the rare occurrence of a flexor digitorum profundus (FDP) avulsion of the left little finger in association with a pathological fracture of an enchondroma. The enchondroma was treated by simple curettage without bone graft. The FDP tendon was re-attached to the distal phalanx using the pull-out technique with a non-absorbable polyethylene suture. We recommend simple curettage without bone grafting in cases of enchondroma of the distal phalanx in which the bone defect is small.

Effects of zinc coadministration on lead toxicities in rats.

In order to investigate the effects of Zn on Pb toxicities. Proportion of abnormal sperm, percentage of micronucleated polychromatic erythrocyte (MPCE), serum thyroid hormones (T(3), T(4)) and cortisol were measured. Rats received intraperitoneal injection of 25 mg/kg Pb acetate, 4 mg/kg Zn acetate, both Pb acetate and Zn acetate, or normal saline as controls, once every two days, 7 times in total. No significant differences in whole blood Pb were detected between groups received Pb alone or both Pb and Zn. On the contrary, the concentration of whole blood Zn in the group given Zn alone was significantly higher than that in the group that received both Pb and Zn. In the groups given Pb alone or both Pb and Zn, proportion of abnormal sperm, frequency of MPCE and serum cortisol were significantly higher than those in controls, whereas serum T(3) and T(4) were significantly lower than in controls. In the group given both Pb and Zn, T(4) was decreased most obviously among the four groups. While the proportion of abnormal sperm was less in the group given both Pb and Zn than in the group given Pb alone. These findings suggest that Zn coadministration might alleviate toxic effects of Pb on the male reproductive system, whereas it could enhance the toxicity on thyroid function. Zn did not affect the toxicities of Pb on cytogenetic systems as indicated by MPCE percentage, and on serum cortisol levels under the dose of the present study. Our results suggested the double-edged effects of Zn on Pb toxicities in different organs. Therefore, the effects of Zn on Pb toxicities should be evaluated systematically.

Comparison of 4', 6'-diamidino-2-phenylindole and Giemsa stainings in preimplantation mouse embryos micronucleus assay including a triple dose study.

Analysis of micronuclei (MN) in preimplantation embryos is a good method for the evaluation of cytogenetic damage induced by occupational and environmental mutagen during early pregnancy. To examine whether conventional Giemsa staining produced the same accuracy of micronuclei as the DNA-specific 4', 6'-diamidino-2-phenylindole (DAPI) staining in preimplantation embryo induced by maternal exposure to chlorpyrifos, we conducted assays on 469 mouse (3 groups) preimplantation embryos micronucleus. Slides were stained with DAPI. After DAPI staining, the slides were de-stained and restained with Giemsa. Giemsa staining showed similar frequencies in MN to DNA-specific DAPI staining in all three groups. Both staining techniques revealed significant increases in frequency of MN in the treated group in comparison to the control group. Both methods showed a statistically significant correlation between MN frequency and the dose of chlorpyrifos. Compared with DAPI staining, the sensitivity of Giemsa staining was 85.0%, 86.0% and 90.9% for control, 40 mg/kg, and 80 mg/kg chlorpyrifos treated group, respectively. The specificity was 97.9%, 91.4% and 96.5% for control, 40 mg/kg, and 80 mg/kg chlorpyrifos treated group, respectively. Thus, we recommend that Giemsa staining technique be a standard staining method in detecting MN of preimplantation embryos induced by occupational or environmental hazards.

Relationship between fetal weight, placental growth and litter size in mice from mid- to late-gestation.

In mammals, the placenta, which consists of maternal and fetal components, is important in fetal development because it supplies the fetus with the nourishment it needs. We investigated the effects of placental growth and litter size on mouse fetal weights from mid- to late-gestation. The mean weight of male fetuses at 13.5 days post coitum (dpc) was larger than that of females. Although there was a significant correlation between fetal and placental weights in both males and females during mid-gestation (P<0.05), there was no correlation during late-gestation. However, a significant correlation was observed between litter size and fetal weights in both males and females at 17.5 dpc (P<0.05). These findings suggest that fetal weight is regulated by placental growth during mid-gestation, while the effects of litter size are more prominent towards late-gestation.

Genotoxic damage in female residents exposed to environmental air pollution in Shenyang city, China.

Air pollution has been suggested to cause genetic damage from investigations of many biological markers that measure cytogenetic damage in humans. Here, we evaluated the genotoxic effects of ambient air pollution by investigating the extent of cytogenetic damage in human blood lymphocytes from rural and industrial female residents of Shenyang city, China, using micronuclei assays and polymorphic analyses of metabolic enzyme and DNA repair genes. After adjustment for potential confounding factors including DNA polymorphisms, industrial female residents were found to have a higher micronuclei frequency. These results provide evidence that micronuclei assays are a sensitive indicator to air pollution-induced genotoxic effects in humans.

Oxidative DNA damage in relation to neurotoxicity in the brain of mice exposed to arsenic at environmentally relevant levels.

To clarify the association between oxidative DNA damage and the neurotoxicity of arsenic, the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) as an index of oxidative DNA damage in the brain was examined in mice fed with drinking water containing 1 or 2 ppm arsenic, using an HPLC-electrochemical detector and immunohistochemical method. 8-OHdG levels were significantly increased in the brain of mice given arsenic and its immunoreactivity was distributed in the cerebral and cerebellar cortexes. Cerebral cortex neurons and Purkinje cells in the cerebellar cortex showed degenerative changes in accordance with the distribution of 8-OHdG immunoreactivity. The levels of arsenic in this study were lower than those reported in epidemiological studies. Thus, we conclude that environmentally relevant levels of arsenic induce pathological changes through oxidative DNA damage in the brain tissues in vivo and that cerebral and cerebellar cortex neurons seem to be the major targets of arsenic neurotoxicity.

Teratogenicity and developmental toxicity of chlorpyrifos. Maternal exposure during organogenesis in mice.

Chlorpyrifos, an organophosphate pesticide, was evaluated for potential teratogenicity and developmental toxicity in mice. Pregnant females were given a single intraperitoneal injection (40 or 80 mg/kg) on day 10 of gestation and fetuses were evaluated on gestation day 17. At 80 mg/kg, chlorpyrifos treatment resulted in a significant reduction in numbers of live fetuses, and increase in resorptions, versus control litters. There was no indication of maternal toxicity. External and skeletal malformations were observed at 80 mg/kg, but not 40 mg/kg. Rates of fetuses with cleft palate increased significantly (p<0.05) following 80 mg/kg chlorpyrifos (5.97%) versus control litters (0.97%). Similarly, the absence of thoracic vertebrae was increased and the number of caudal vertebrae was significantly decreased. It is suggested that chlorpyrifos is teratogenic and embryotoxic in mice at doses below those that cause significant maternal toxicity.

Effects of prednisolone and complex of vitamin B1, B2, B6 and B12 on organophosphorus compound-induced delayed neurotoxicity.

Protective effects of prednisolone as a synthetic adrenal cortical hormone and complex of vitamin B(1), B(2), B(6) and B (12) on organophosphorus compound-induced delayed neurotoxicity (OPIDN) caused by leptophos and tri-o-cresyl phosphate (TOCP) as organophosphates (OPs) were examined. Nine groups of hens (six for each) were used. Eight groups received intravenous injection of 30 mg/kg of leptophos or 40 mg/kg of TOCP (four groups in each). Among them, three groups which received leptophos were given (p.o.) predonisolone (2 mg/body), vitamin B complex (25 mg/body) or both 3 h after OPs injection and then every day for 15 d (one group for each); the same treatment was performed on three groups which received TOCP. The remaining one group served as controls. It was observed that delayed neuropathy induced by OPs could not be resisted completely by the treatment with prednisolone or vitamin B complex, but clinical signs of OPIDN and pathological changes in hens that received these two protective agents after OPs were less severe than those in hens that received only OPs. Of these groups, the improvement in clinical signs was best shown in hens that received the both two protective agents. In addition, improvement in clinical signs among the hens that did not deteriorate to paralysis was observed. In particular, those which developed mild ataxia recovered well. It is indicated that combining administration of prednisolone and vitamin B complex early before clinical signs are manifest is effective in alleviating neuropathy. It is also suggested that recovery or good prognosis will be expected, as long as progression of the clinical signs is prevented before paralysis develops in delayed neuropathy.

Evidence of association of the CYP2E1 genetic polymorphism with micronuclei frequency in human peripheral blood.

Micronuclei (MN) are used as one of the cytogenetic biomarkers, and intra- and inter-individual variations in this frequency have been reported in human blood lymphocytes. Polymorphisms in a few metabolic enzyme genes seem to account for a proportion of this variability, but the impacts of specific genetic variants on the MN frequency have not yet been clarified. Here, we investigated the relationship between the MN frequency and several gene polymorphisms in 90 healthy Japanese men. The subjects with the CYP2E1(*)3 variant allele had a statistically lower mean MN frequency than subjects with the CYP2E1(*)1/(*)1 wild type. Furthermore, the adjusted odds ratio (OR) of the CYP2E1(*)3 variant with higher MN frequency levels was also significantly lower and calculated to be 0.25 (95% CI 0.07-0.83), when the OR for the subjects with the CYP2E1(*)1/(*)1 wild type was defined as 1.00. These data suggest that the CYP2E1(*)3 polymorphism may have the potential to influence the baseline frequency of MN.

Advanced Kienböck's disease treated with implantation of a tendon roll and temporary partial fixation of the wrist.

Twenty-one patients with advanced Kienböck's disease were treated by implantation of a tendon roll and temporary partial fixation of the wrist. There were 13 women and eight men. Their ages at the time of operation ranged from 24 to 72 years. According to Alexander and Lichtman's classification, 12 patients were stage IIIb and nine stage IV. After implantation of the tendon roll, the scaphotrapezio-trapezoidal joint was fixed with Kirschner wires in 19 patients, and the scaphocapitate joint with absorbable pins in two. Postoperative wrist pain disappeared in nine patients and was reduced in 12. The mean postoperative total arc of flexion and extension of the wrist increased from 91 degrees to 103 degrees, and mean grip strength improved from 11.5 to 17.2 kg. Loosening of Kirschner wires during partial fixation of the wrist was seen in six cases, and required early removal of the loose wires.

Effects of ALDH2 gene polymorphisms and alcohol-drinking behavior on micronuclei frequency in non-smokers.

Alcohol abuse is a serious health problem, leading to life-threatening damage to most of the important organ systems. Genotoxic damage is used as an early effect indicator in the surveillance of human exposure to genotoxic substances. Intra- and inter-individual variations of baseline frequencies of micronuclei (MN) in peripheral blood lymphocytes of human populations have been reported previously. Polymorphisms in a few metabolic enzyme genes seem to account for a proportion of this variability, but the impact of specific genetic variants on MN frequencies has not yet been clarified. In 42 healthy Japanese non-smoking men, we investigated the relationship between the MN frequency levels and genetic polymorphisms in three different genes: aldehyde dehydrogenase 2 (ALDH2), X-ray repair cross-complementing group 1 (XRCC1) and excision repair cross-complementing group 2 (ERCC2). Genotyping was performed by PCR-RFLP analysis. The ALDH2 variant (deficient-type) was significantly associated with increased MN frequency levels in subjects with drinking more than three times per week, whereas the XRCC1 and ERCC2 variants seemed to be unrelated to the MN frequency. The ALDH2-deficient habitual drinkers had an average MN frequency of 5.88+/-0.58 (+/- S.E.) compared with 3.20 +/- 0.80 in the ALDH2-proficient habitual drinkers (P<0.05). The ALDH2-proficient non-habitual drinkers had the lowest MN frequency (1.56 +/- 0.41). Furthermore, subjects with highest levels of mean MN frequency, who consumed more than 100g of alcohol per week and more than three times per week, had A2 genotype of ALDH2. A significant odds ratio (12.25, P<0.05) for the MN frequency levels above the 50th percentile value was observed for the ALDH2-deficient individuals versus the ALDH2-proficient individuals after adjustment for several confounders. These results strongly suggest that human early genotoxic effect studies based on the cytogenetic markers of MN should take into account both the individual ALDH2 polymorphism and the potential confounding effect of the drinking behavior.

Subacute toxic effects of zinc on various tissues and organs of rats.

In order to expand our knowledge of zinc toxicity and to assess further the toxicities of zinc systematically, we observed the toxic effects of zinc on the functions of various tissues and organs in rats. The rats were randomly divided into four groups (14 in each group), viz. one normal control group (received saline), two zinc groups (Znlow: 4 mg/kg of zinc acetate; Znhigh: 8 mg/kg of zinc acetate), and one cyclophosphamide group (50 mg/kg, as positive control of micronucleated polychromatic erythrocytes (MPCEs)). Saline and zinc acetate were administered intraperitoneally to the rats once every 2 days, seven times in total. Cyclophosphamide was given intraperitoneally to the rats once. The concentration of blood zinc was determined and accumulation of zinc was not observed in the experimental groups. The frequencies of basophilic stippled erythrocyte (BSE) and MPCEs in the Znhigh group were significantly higher than those in the control group (P<0.05). The levels of serum glutamic oxalacetic transaminase (GOT) and serum triiodothyronine (T3) in the Znhigh groups decreased significantly, compared with the control group (P<0.01 or 0.05). Moreover, we also observed that the level of serum cortisol, another adrenal corticoid hormone in rats, was increased by zinc acetate in a dose-dependent manner. According to the literature and our findings, exposure to zinc, especially at higher doses, may produce toxic effects on various tissues and organs including the hematopoietic system, cytogenetics, biochemistry and endocrine system function. Therefore, it is suggested that zinc should be used carefully, especially by high risk groups such as children and pregnant women despite its use as a food additive or in self-medication. At the same time, it is necessary to investigate and research further these toxicities of zinc with long-term administration of low dosage.

The effect of Calcicol as calcium tonic on delayed neurotoxicity induced by organophosphorus compounds.

To examine whether delayed neuropathy is prevented or alleviated when Ca is administered to experimental animals before or after organophosphorus compounds (OPs) dosing, we observed the effects of Calcicol administration as a calcium tonic on delayed neurotoxicity by OPs in hens. The hens (n=28) were randomly divided into seven groups (four in each group). One group received glycerol formal as vehicle group, two groups received 30 mg/kg leptophos or 40 mg/kg triortho-cresyl phosphate (TOCP) (L group and T group), two groups received 2.4 mg/kg Ca(2+) (0.3 ml/kg Calcicol) 24 h before leptophos or TOCP administration, and the last two groups received 2.4 mg/kg Ca after leptophos or TOCP administration, respectively. Although delayed polyneuropathy induced by OPs could not be prevented completely by Calcicol, the clinical signs of organophosphorus-induced delayed neuropathy (OPIDN) in hens that received Calcicol soon before or after OPs administration were less severe than those in hens that received only OPs and there were significant differences in OPIDN score between groups (P<0.05). This shows that polyneuropathy and the recovery function of nerves and muscles suffering from polyneuropathy can be alleviated, as long as calcium tonic is administered before the clinical signs develop. This study offers hope of recovery to humans who are exposed to these OPs because of work, attempted suicide, accidental ingestion or other accidents, etc. Meanwhile, our results indicate further that there is a relationship between a decrease in Ca(2+) concentration in tissues and induction of delayed neuropathy.