Action mechanisms of probiotics on Candida spp. and candidiasis prevention: an update.

Due to the high incidence of fungal infections caused by Candida species and their increasing resistance to antimicrobial treatments, alternative therapies such as probiotics have been studied. It has been show that several species of the genus Lactobacillus have anti-Candida activity, probably by direct inhibition, through competition for adhesion sites or production of secondary metabolites, and by indirect inhibition, through stimulation of the immune system of their host. However, the mechanisms of inhibition of these probiotics on Candida species have not yet been fully elucidated since this effect is related to more than one inhibition pathway. In the literature, several in vitro and in vivo studies have been developed seeking to elucidate the probiotics mechanisms of action. These studies have been focused on C. albicans inhibition assays, including analysis of antimicrobial activity, adherence capacity, biofilms formation, filamentation and interference on virulence genes, as well as assays of experimental candidiasis in invertebrate and vertebrate models. In this context, the purpose of this review was to gather different studies focused on the action mechanism of probiotic strains on Candida sp. and to discuss their impact on the candidiasis prevention.

Lactobacillus rhamnosus inhibits Candida albicans virulence factors in vitro and modulates immune system in Galleria mellonella.

AIM: The aim of this study was to evaluate the potential anti-Candida effects of Lactobacillus rhamnosus ATCC 9595 on Candida albicans ATCC 18804 using in vitro and in vivo models. METHODS AND RESULTS: The in vitro analysis evaluated the effects of L. rhamnosus on C. albicans's biofilm formation by CFU count and metabolic activity, filamentation capacity, and adhesion (ALS3 and HWP1) and transcriptional regulatory gene (BCR1 and CPH1) expression. The in vitro results showed that both the L. rhamnosus cells and supernatant reduced C. albicans biofilm formation, filamentation and gene expression. In the in vivo study, the treatment with L. rhamnosus supernatant increased 80% the survival of Galleria mellonella larvae infected with C. albicans. Furthermore, the supernatant of L. rhamnosus recruited haemocytes into the haemolymph (2·1-fold increase). CONCLUSIONS: Lactobacillus rhamnosus reduced the biofilm formation and filamentation of C. albicans in vitro by negatively regulating all studied C. albicans genes. Lactobacillus rhamnosus protected G. mellonella against experimental candidiasis in vivo. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first study to report the anti-Candida properties of L. rhamnosus ATCC 9595. The supernatant of this strain has immunomodulatory effects on the G. mellonella model and protects the larvae against pathogens.

Photodynamic inactivation of biofilms formed by Candida spp., Trichosporon mucoides, and Kodamaea ohmeri by cationic nanoemulsion of zinc 2,9,16,23-tetrakis(phenylthio)-29H, 31H-phthalocyanine (ZnPc).

The biofilms formed by opportunistic yeasts serve as a persistent reservoir of infection and impair the treatment of fungal diseases. The aim of this study was to evaluate photodynamic inactivation (PDI) of biofilms formed by Candida spp. and the emerging pathogens Trichosporon mucoides and Kodamaea ohmeri by a cationic nanoemulsion of zinc 2,9,16,23-tetrakis(phenylthio)-29H,31H-phthalocyanine (ZnPc). Biofilms formed by yeasts after 48 h in the bottom of 96-well microtiter plates were treated with the photosensitizer (ZnPc) and a GaAlAs laser (26.3 J cm(-2)). The biofilm cells were scraped off the well wall, homogenized, and seeded onto Sabouraud dextrose agar plates that were then incubated at 37°C for 48 h. Efficient PDI of biofilms was verified by counting colony-forming units (CFU/ml), and the data were submitted to analysis of variance and the Tukey test (p < 0.05). All biofilms studied were susceptible to PDI with statistically significant differences. The strains of Candida genus were more resistant to PDI than emerging pathogens T. mucoides and K. ohmeri. A mean reduction of 0.45 log was achieved for Candida spp. biofilms, and a reduction of 0.85 and 0.84, were achieved for biofilms formed by T. mucoides and K. ohmeri, respectively. Therefore, PDI by treatment with nanostructured formulations cationic zinc 2,9,16,23- tetrakis (phenylthio)- 29H, 31H- phthalocyanine (ZnPc) and a laser reduced the number of cells in the biofilms formed by strains of C. albicans and non-Candida albicans as well the emerging pathogens T. mucoides and K. ohmeri.

Antimicrobial photodynamic therapy: photodynamic antimicrobial effects of malachite green on Staphylococcus, enterobacteriaceae, and Candida.

OBJECTIVE: This study investigated in vitro the photodynamic antimicrobial effects of the photosensitizer malachite green on clinical strains of Staphylococcus, Enterobacteriaceae, and Candida. MATERIALS AND METHODS: Thirty-six microbial strains isolated from the oral cavity of patients undergoing prolonged antibiotic therapy, including 12 Staphylococcus, 12 Enterobacteriaceae, and 12 Candida strains, were studied. The number of cells of each microorganism was standardized to 10(6) cells/mL. Twenty-four assays were carried out for each strain according to the following experimental conditions: gallium-aluminum-arsenide laser and photosensitizer (n = 6, L+P+), laser and physiologic solution (n = 6, L+P-), photosensitizer (n = 6, L-P+), and physiologic solution (n = 6, L-P-). Next, cultures were prepared on brain-heart infusion agar for the growth of Staphylococcus and Enterobacteriaceae, and on Sabouraud dextrose agar for the growth of Candida, and incubated for 48 h at 37 degrees C. The results are reported as the number of colony-forming units (CFU/mL) and were analyzed with analysis of variance and the Tukey test. RESULTS: The Staphylococcus, enterobacterial, and Candida strains were sensitive to photodynamic therapy with malachite green (L+P+). A reduction of approximately 7 log(10) for Staphylococcus, 6 log(10) for enterobacteria, and 0.5 log(10) for the genus Candida. Significant statistical differences were observed between the L+P+ groups and the control groups (L-P-). CONCLUSION: The Staphylococcus, Enterobacteriaceae, and Candida strains studied were sensitive to photodynamic therapy with malachite green.

Sexual dimorphism and seasonal variation in submandibular gland histology of Bolomys lasiurus (Rodentia, Muridae).

Wild rodents (Bolomys lasiurus) of both sexes were caught in a cerrado grassland area during the dry (July-September) and rainy (January-March) seasons of Brazil. Fasted animals were perfused with Karnovsky fixative through the left ventricle, under ether anesthesia, and the submandibular gland was processed for embedding in historesin. Histological and histometric data show sexual dimorphism at both seasons. In the volume percentage of the granular convoluted tubules (GCT) and their secretory granules, the males exhibited higher values. The absolute volume occupied by these structures, however, was dimorphic only in the rainy season. The diameter of the GCT, the height of its epithelium, and its total length were also greater in males during the rainy season. The absolute volumes of the acini and of the ductal tree were identical in both sexes in the dry and rainy seasons but the acinar diameter increased in the males and females during the rainy season. The sexual dimorphism and the seasonal variations now described in the B. lasiurus submandibular glands could be explained by the augmented reproductive activity of the males in the rainy period.

Mechanisms underlying the structural alterations of the rat submandibular gland induced by Tityus serrulatus tityustoxin.

As the mechanisms underlying the structural changes induced in rat submandibular glands by Tityus serrulatus tityustoxin have not been reported, the present study was undertaken to investigate the participation of adrenergic and muscarinic cholinergic receptors in these alterations. Most of the stimulatory effects of the toxin are observed in the secretory cells of the acini and granular convoluted tubules (GCT). We evaluated the ability of the toxin to induce morphological changes in acinar and GCT cells after adrenoreceptor and cholino receptor blockage. The influence of tityustoxin-induced adrenal discharge on the acinar and GCT cells was also investigated after bilateral adrenalectomy. We show that the intense cytoplasmic vacuolation of the acinar cells induced by tityustoxin was prevented by prazosin (alpha(1) adenoreceptor blockade) and atropine (muscarinic cholinoreceptor blockade). The decrease of GCT cell granules following tityustoxin injection was completely blocked by prasozin and partially by propranolol. These results indicate that acinar vacuolation, degranulation of GCT cells, reduction of GCT diameter and height of its epithelium depends on tityustoxin induced adrenergic and cholinergic mechanisms. In contrast, tityustoxin induced acinar cell degranulation was not modified by atropine, prasozin or propranolol (beta(1)-beta(2) adenoreceptor blockade). Thus, acinar degranulation seems to be due to a direct action of tityustoxin on of the rat submandibular glands. The degranulation of the GCT cells and the acinar vacuolation was also prevented by bilateral adrenalectomy, suggesting that these effects are mostly due to catecholamines released from the adrenal glands.

Leigh disease: clinical, neuroradiologic, and biochemical study of three new cases with cytochrome c oxidase deficiency.

Three cases of Leigh disease are described. In all three, symptoms began in the first months of life, with muscle hypotonia, lactic acidosis, and psychomotor delay. The diagnosis was made on the basis of the clinical characteristics, biochemical abnormalities, and typical brain magnetic resonance imaging with symmetric lesions suggesting bilateral necrosis at the level of the basal ganglia and of the midbrain. Cytochrome c oxidase (complex IV of the mitochondrial respiratory chain) deficiency was demonstrated in muscle tissue in all patients and confirmed in skin fibroblasts in patient 3. A genetic heterogeneity was present in these patients since only one had a SURF-1 gene mutation. The clinical, biochemical, and neuroradiologic aspects are discussed. Finally, the finding of facial dysmorphisms in the cytochrome c oxidase deficiency observed in one of the described cases is of extreme interest; to our knowledge, this association has never been reported in the literature.

Effects of crude venom, tityustoxin and toxin Ts-gamma from Tityus serrulatus scorpion on secretion and structure of the rat submandibular gland.

Changes in the rat submandibular glands after intravenous injections of Tityus serrulatus scorpion venom, tityustoxin or toxin Ts-gamma were studied histologically and morphometrically. The acini and the granular convoluted tubules presented the most prominent changes. The following variables were measured: (a) relative volume occupied by the glandular structures; (b) diameter of the granular convoluted tubules and thickness of their epithelium; (c) diameter of the acini. The cytoplasm of the acinar cells was extensively occupied by large confluent vacuoles and had a reduced number of secretory granules after intravenous injections of venom or toxins. The morphological changes caused by toxin Ts-gamma were greater than those evoked by tityustoxin or crude venom injections. In spite of the changes in acinar cells, acinar diameter showed no significant alterations after venom or toxin injections. Reduction of diameter and depletion of the cytoplasmic secretory granules were observed in the granular convoluted tubules 2 h after intravenous injections of crude venom, or after 1 h with tityustoxin or toxin Ts-gamma. The intravenous injection of crude venom did not induce any visible change in the granular convoluted tubules after 1 h. These structural changes could explain the concomitant intense sialagogue effect elicited by crude venom, tityustoxin and toxin Ts-gamma. The sialagogue effect induced by toxin Ts-gamma was larger than those induced by crude venom or tityustoXin.

Autonomic innervation of the salivary glands in cebid monkeys: a histochemical study.

The autonomic innervation of the major and minor salivary glands was studied in five species of cebid monkeys using acetylcholinesterase (AChE) and catecholamine histochemistry. Catecholamine-containing and AChE-positive nerve fibres were observed in the vessels and secretory endpieces of all glands, with no apparent predominance of one type over the other. In the intralobular ducts, however, the cholinergic innervation predominates. In the major salivary and minor sublingual glands the density of the nervous supply was higher, whereas in the secondary mandibular and posterior lingual glands it was less dense. The morphological patterns of salivary gland innervation found in Cebidae are compared with those of the related family Callitrichidae.

The addition of an air/water button to a flexible bronchoscope (provided with a suction button) for use as a slim operative panendoscope.

Thin-caliber (4.9 and 6.3 mm) flexible bronchoscopes already provided with a suction button have been modified by adding an air/water button for the control of air insufflation and water irrigation; the channel used is the biopsy-suction one. With the aid of this instrument, several pathologies can be studied and treated, under adverse conditions such as esophageal or recto-sigmoidal stenosis, hematuria in polytraumatic patients, residual stones in patients carrying a T-tube, acute respiratory obstructions, etc.

A percussion lithotripter.

A mechanical lithotripter producing a percussion action on biliary stones is described. This device seems to be robust and flexible at the same time. Every biliary stone is easily crushed by this lithotripter. Sixty-seven patients have been endoscopically treated with the aid of this probe.

Use of a nonselective beta-blocker, nadolol, in the treatment of portal hypertension in cirrhotics.

Recently a medical treatment with propranolol has been proposed in order to decrease portal pressure and lessen the risk of recurrent gastrointestinal bleeding in cirrhotic patients. No data are available about another beta-blocker, nadolol, which, unlike propranolol, has a low hepatic metabolism, a low lipid solubility, a long serum half-life and does not reduce renal blood flow in patients with arterial hypertension. In 18 cirrhotics with portal hypertension, the effects of nadolol were studied on systemic and hepatic haemodynamics and liver function, at a dosage which reduced the heart rate by 25%. After one month of treatment, a significant decrease in cardiac output, portohepatic gradient and estimated hepatic blood flow were found. The degree of oesophageal varices was reduced in 11 patients, unchanged in the other seven. Hepatic function, evaluated by galactose eliminating capacity, did not change significantly. Although the small number of treated patients does not allow definitive conclusions, nadolol seems to have the features needed to be used in the medical treatment of portal hypertension in patients with liver cirrhosis.