Cooperation of Blm and Mus81 in development, fertility, genomic integrity and cancer suppression.

BLM is a DNA helicase important for the restart of stalled replication forks and for homologous recombination (HR) repair. Mutations of BLM lead to Bloom Syndrome, a rare autosomal recessive disorder characterized by elevated levels of sister chromatid exchanges (SCEs), dwarfism, immunodeficiency, infertility and increased cancer predisposition. BLM physically interacts with MUS81, an endonuclease involved in the restart of stalled replication forks and HR repair. Herein we report that loss of Mus81 in Blm hypomorph mutant mice leads to infertility, and growth and developmental defects that are not observed in single mutants. Double mutant cells and mice were hypersensitive to Mitomycin C and γ-irradiation (IR) compared with controls and their repair of DNA double-strand breaks (DSBs) mediated by HR pathway was significantly defective, whereas their non-homologous-end-joining repair was elevated compared with controls. We also demonstrate the importance of the loss of the nuclease activity of Mus81 in the defects observed in Mus81(-/-) and double mutant cells. Exacerbated IR-induced chromosomal aberration was observed in double mutant mice and despite their reduced SCE levels, these mutants showed increased tumorigenesis risks. Our data highlight the importance of Mus81 and Blm in DNA DSB repair pathways, fertility, development and cancer.

Remarkable transition from rocksalt/perovskite layered structure to fluorite/rocksalt layered structure in rapidly cooled Ln2CuO4.

Lanthanide cuprates of formula Ln2CuO4 exist in two principal forms, T and T' which are renowned for their exhibition at low temperatures of hole and electronic types of superconductivity, respectively. These structures differ primarily in the arrangement of oxygen between the perovskite layers and also in nature of the copper oxygen planes. The Cu-O distance in the T structure (~1.90 Å) is much shorter than the T' (1.97Å), reflecting a transition between partial Cu⁺and partial Cu³âº character. In seeking to find compositions that bridge these two structure/electron carrier types, we observed the transition from a T structure to a T' type structure, resulting in the metastable form T″ with slightly larger volume but similar character to T'. This transition from T to T″ is associated with 5% increase in a and a 5% decrease in c parameters of the tetragonal unit cells, which results in disintegration of ceramic bodies.

Oregano and clove essential oils induce surface alteration of Saccharomyces cerevisiae.

The antimicrobial properties of volatile aromatic oils have been recognized since antiquity. Oregano and clove oils have been shown to possess a broad spectrum of antimicrobial activity. In this paper, the fungicidal action of these two essential oils was studied on the yeast model Saccharomyces cerevisiae. Yeast cell lysis was shown by the release of substances absorbing at 260 nm. In addition, scanning electron microscopy analyses revealed that the surface of treated cells by oregano and clove oils was significantly damaged.

Study of anticandidal activity of carvacrol and eugenol in vitro and in vivo.

BACKGROUND/AIMS: The mechanism of the anticandidal action of the major phenolic components of oregano and clove essential oils - carvacrol and eugenol - was studied. This activity was also evaluated for the therapeutic efficacy in the treatment of the experimental oral candidiasis induced by Candida albicans in immunosuppressed rats. METHODS: In vitro, the addition of carvacrol at 0.1% or eugenol at 0.2% during the exponential growth of C. albicans was evaluated. The release of substances absorbing at 280 nm by cells treated with these two components was also measured spectrophotometrically. In vivo, oral candidiasis in immunosuppressed rats was established by inoculating 3 x 10(8) cells of C. albicans with a cotton swab on three alternate days. The number of colony counts was evaluated from the oral cavity of rats treated for eight consecutive days with carvacrol, eugenol or nystatin and compared to untreated controls. RESULTS: Carvacrol and eugenol were fungicidal in exponentially growing C. albicans. Interestingly, this fungicidal effect was accompanied by the release of substances absorbing at 280 nm. In an immunosuppressed rat model of oral candidiasis, carvacrol or eugenol treatment significantly (P < 0.05) reduced the number of colony counts sampled from the oral cavity of rats treated for eight consecutive days compared to untreated control rats. Similar results were obtained with nystatin used as a reference treatment. CONCLUSION: The in vitro results indicated that both carvacrol and eugenol exerted an anticandidal effect by a mechanism implicating an important envelope damage. Their in vivo efficacy on experimental oral candidiasis leads us to consider them as possible antifungal agents.

Antifungal treatment with carvacrol and eugenol of oral candidiasis in immunosuppressed rats.

Carvacrol and eugenol, the main (phenolic) components of essential oils of some aromatic plants, were evaluated for their therapeutic efficacy in the treatment of experimental oral candidiasis induced by Candida albicans in immunosuppressed rats. This anticandidal activity was analyzed by microbiological and histopathological techniques, and it was compared with that of nystatin, which was used as a positive control. Microbiologically, carvacrol and eugenol significantly (p<0.05) reduced the number of colony forming units (CFU) sampled from the oral cavity of rats treated for eight consecutive days, compared to untreated control rats. Treatment with nystatin gave similar results. Histologically, the untreated control animals showed numerous hyphae on the epithelium of the dorsal surface of the tongue. In contrast no hyphal colonization of the epithelium was seen in carvacrol-treated animals, while in rats treated with eugenol, only a few focalized zones of the dorsal surface of the tongue were occupied by hyphae. In the nystatin treated group, hyphae were found in the folds of the tongue mucosa. Thus, the histological data were confirmed by the microbiological tests for carvacrol and eugenol, but not for the nystatin-treated group. Therefore, carvacrol and eugenol could be considered as strong antifungal agents and could be proposed as therapeutic agents for oral candidiasis.

Evaluation of carvacrol and eugenol as prophylaxis and treatment of vaginal candidiasis in an immunosuppressed rat model.

OBJECTIVES: Anticandidal activity of carvacrol and eugenol, the major phenolic components of oregano and clove essential oils, respectively, were tested in vivo. METHODS: Efficacy evaluation of carvacrol and eugenol in the prophylaxis and treatment of experimental vaginal candidiasis was performed in immunosuppressed rats. The anticandidal activity was analysed by microbiological and histological techniques and was compared with that of nystatin. RESULTS: Microbiologically, prophylactic treatment with carvacrol eradicated the vaginal fungal burden of infected rats, whereas eugenol reduced the number of colony counts of Candida albicans in vaginas of infected rats by 98.9% 10 days after inoculation. Therapeutic treatment for 7 consecutive days with carvacrol was able to eradicate the vaginal candidal burden in 7/9 of the infected rats and reduced the number of colony counts of C. albicans in vaginas of the two remaining rats by 98%. Treatment with eugenol completely cured 2/9 of the infected animals, but the 7/9 still infected showed an 84% reduction of colony counts of C. albicans in their vaginas. Histologically, in all treated rats, no Candida organisms were found in the lumina of the vagina; this was in contrast to control groups in which many yeasts, strongly stained with periodic acid-Schiff, were observed. The results obtained with nystatin used at 10-fold minimal inhibitory concentration confirm the validity of this model. CONCLUSIONS: Carvacrol and eugenol could be considered as promising products in the treatment of vaginal candidiasis. This work is a preliminary contribution to the development of a new generation of efficient and natural antifungal agents for curative treatment and prophylaxis.

Antifungal treatment with carvacrol and eugenol of oral candidiasis in immunosuppressed rats

Carvacrol and eugenol, the main (phenolic) components of essential oils of some aromatic plants, were evaluated for their therapeutic efficacy in the treatment of experimental oral candidiasis induced by Candida albicans in immunosuppressed rats. This anticandidal activity was analyzed by microbiological and histopathological techniques, and it was compared with that of nystatin, which was used as a positive control. Microbiologically, carvacrol and eugenol significantly (p<0.05) reduced the number of colony forming units (CFU) sampled from the oral cavity of rats treated for eight consecutive days, compared to untreated control rats. Treatment with nystatin gave similar results. Histologically, the untreated control animals showed numerous hyphae on the epithelium of the dorsal surface of the tongue. In contrast no hyphal colonization of the epithelium was seen in carvacrol-treated animals, while in rats treated with eugenol, only a few focalized zones of the dorsal surface of the tongue were occupied by hyphae. In the nystatin treated group, hyphae were found in the folds of the tongue mucosa. Thus, the histological data were confirmed by the microbiological tests for carvacrol and eugenol, but not for the nystatin-treated group. Therefore, carvacrol and eugenol could be considered as strong antifungal agents and could be proposed as therapeutic agents for oral candidiasis.

Surface alteration of Saccharomyces cerevisiae induced by thymol and eugenol.

AIMS: This study aims to bring some information about the mechanism of the fungicidal action of thymol and eugenol; phenolic major components of thyme and clove essential oils respectively. Saccharomyces cerevisiae was used as yeast model. METHODS AND RESULTS: Treatment of yeast cells with these components led to their lysis as shown by the release of substances absorbing at 260 nm. In addition, scanning electron microscope observations revealed that the surface of the treated cells was significantly damaged. CONCLUSIONS: Antifungal activity of thymol and eugenol involve alteration of both membrane and cell wall of the yeast. SIGNIFICANCE AND IMPACT OF THE STUDY: This work is a preliminary contribution aiming to develop a new generation of efficient and natural antifungal agents.

Tyrosine hydroxylase and dopamine beta-hydroxylase inductions evoked by reserpine in the superior cervical ganglion of developing eu- and hypothyroid rats.

This study was designed to determine the effect of neonatally-produced hypothyroidism on reserpine-elicited tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (D beta H) induction in the superior cervical ganglion (SCG) in rats. Some rats were rendered hypothyroid from birth by daily treatment with propylthiouracil (PTU). Some hypothyroid rats received replacement therapy with triiodothyronine (T3). Some rats received PTU for 20 days, beginning at 90 days of age. Some rats were not treated and served as controls. TH and D beta H activities were assayed at 30, 50 and 110 days of age. Basal TH activity in the SCG for rats made hypothyroid as neonates was significantly lower than for controls at all ages tested; basal D beta H activity for these rats was lower than for controls at 30 and 50 days of age, but by 110 days was not different from that for controls. Basal TH activity for rats made hypothyroid as adults was intermediate between that for controls and rats made hypothyroid from infancy. Injecting control rats with reserpine produces a robust TH induction in the SCG at each age tested, and a strong D beta H induction at 50 and 110 days of age. Reserpine-evoked TH and D beta H inductions in rats made hypothyroid as adults were not different from those seen in controls. In contrast, rats made hypothyroid from infancy showed virtually no evidence of a reserpine-provoked TH or D beta H induction at any age tested. TH and D beta H inductions for hypothyroid rats given T3 replacement were completely normal.(ABSTRACT TRUNCATED AT 250 WORDS)

The surgical treatment of noma.

Noma is a gangrenous stomatitis affecting children from developing countries. It may leave dreadful mutilations around the mouth, with amputation of the lips, cheek, nose, lids, maxilla, palate, or mandibula. Reconstruction should take into account the size of the defect, the presence of trismus or constriction of the mandible, the age of the child, and the child's general condition. During the last 3 years, eight patients were treated at the Unit of Plastic and Reconstructive Surgery of the Hôpital Cantonal Universitaire. Except in one case, tracheostomy was avoided, thanks to intranasal intubation by fibroscopy. These children, aged 2 to 9 years, underwent 31 general anesthesias and complex reconstructive procedures, including latissimus dorsi musculocutaneous pedunculated and free flaps, cranial flaps with galea, cranial bone and skin grafts, and retroauricular temporal skin flaps. All patients were able to return to Africa with dramatic functional and cosmetic improvements. However, satisfactory mouth opening and mandibular function were not always obtained.

Influence of hypothyroidism on the ontogenic development of tyrosine hydroxylase induction in the adrenal glands of the rat.

The ontogenic development of the transsynaptic induction of adrenal tyrosine hydroxylase (TH), evoked by reserpine and nicotine was studied in control and hypothyroid young rats, aged 3-52 days. The enzymatic induction was measured as an increase in the enzyme activity, since this increase was shown to be impaired either by an inhibitor of RNA synthesis or by a ganglionic blocker. In the control animals, TH induction elicited by reserpine increases between 3 and 32 days of age. In the hypothyroid rats, the enzymatic induction is impaired up to 32 days; at 52 days the induction is similar in both groups of animals. When nicotine is used as a stimulating agent, hypothyroidism still impairs the enzymatic induction at 5 and 21 days, indicating that at least one of the mechanisms inhibited by hypothyroidism is localized in the adrenal chromaffin cells. The present results, taken together with previous findings dealing with adrenal epinephrine secretion, show that the thyroid hormones play a crucial role in the responses of the adrenal medulla to a stimulation in the developing rat, while they have no effect in the adult.

Developmental pattern of dopamine beta-hydroxylase induction in the adrenals of the rat. Influence of neonatal hypothyroidism.

The extent of dopamine beta-hydroxylase induction elicited by reserpine was measured in young rats rendered hypothyroid from birth and in controls. Hypothyroidism impairs adrenal dopamine beta-hydroxylase induction in the young rat up to 50 days of age and also in the adult. In contrast, hypothyroidism has practically no effect on brainstem dopamine beta-hydroxylase induction.