Relationship between serum and saliva antibodies to Candida and isolation of Candida species from the mucosa of HIV-infected individuals

Colonisation and infection by Candida species occur frequently in acquired immunodeficiency syndrome (AIDS), but their relationship to the humoral immunity against candidiasis is controversial. To evaluate the levels of antibodies to Candida in the serum and in the saliva of HIV-1-infected patients in relation to the presence of immunodeficiency, oral candidiasis and Candida colonisation, Candida was investigated in the urine and in the oral and anal mucosae of HIV-1-infected patients, AIDS patients and healthy controls. The levels of IgG, IgM and IgA antibodies to Candida were determined in the serum and in the saliva by immunoassay. Candida species were detected in 76% of the patients. Mucosal yeast colonisation and the levels of serum and saliva antibodies to Candida were similar between asymptomatic HIV-infected and non-infected patients. Mucosal colonisation was highest in AIDS patients, who also had higher serum IgA and saliva IgG antibodies. Antibody levels were similar in patients with and without candidiasis oral lesions. Asymptomatic HIV-infected individuals are similar to non-infected individuals with respect to mucosal colonisation as well as serum and saliva levels of antibodies to Candida. The higher mucosal colonisation and clinical candidiasis observed in the AIDS patients apparently stimulated a more intense humoral response to the yeast.

Oral lesions in HIV infected individuals from Ribeirao Preto, Brazil

Objectives: The aim of this study was to diagnosis oral lesions related to HIV infection in individuals followed in the General Hospital of the School of Medicine of Ribeirao Preto, University of Sao Paulo, Brazil. The presence of oral lesions was correlated with gender, age, smoking habit, levels of CD4 lymphocytes, HIV load, time of HIV seropositivity, AIDS condition, use of removable dental prosthesis, and use of HAART. Materials and Methods: 340 HIV infected individuals were selected for this study, all participants of the study were examined by only one practiced dentist which performed anamnesis, peribuccal and oral examination. Results: Oral lesions were observed in 113 of 340 (33.2%) HIV infected individuals. These oral lesions included: oral candidiasis (17.7%) of pseudomembranous (10.8%) and of erythematous types (6.9%), angular cheilitis (13.9%), hairy leukoplakia (11.8%), and oral ulcers (2.1%). Oral candidiasis lesions were more frequently observed in women (p. 033). Smoking addict participants presented a high frequency of tongue hairy leukoplakia (p. 038) and a reduced frequency of oral ulcers (p. 018). Hairy leukoplakia and pseudomembranous candidiasis were inversely correlated to CD4+ L levels and directly correlated with HIV load, behaving as immune depression markers. Hairy leukoplakia and pseudomembranous candidiasis also showed an inverse correlation with HAART use (p < .0001). Patients using mobile dental prosthesis presented a high frequency of erythematous candidiasis (p. 003). Conclusion: The inverse correlation with CD4+ L level and the direct correlation with HIV load suggest that oral lesions could be used as alternative clinical markers for poor immune condition in HIV infected individuals.

Efficacy and tolerance of metronidazole and miconazole nitrate in treatment of vaginitis

Objective: To evaluate the efficacy and tolerability of a vaginal pessary containing 750 mg of metronidazole and 200 mg of miconazole nitrate used daily for 7 days in the treatment of vaginitis. Methods: Ninety-two women with vaginitis participated in this phase 3 study using one vaginal pessary daily for 7 days. Gynecological and microbiological evaluations were carried out prior to and following treatment. Results: Reductions occurred in symptoms and signs of vaginitis. Clinical cure rate was 87.7%, while the cure rates according to microscopy and Candida albicans culture were 81.8% and 73.9%, respectively. The cure rate for bacterial vaginosis was 75% and culture of Gardnerella vaginalis turned negative in 63.6% of cases following treatment. The medication was well tolerated. Conclusion: Use of a combination of 750 mg of metronidazole and 200 mg of miconazole in a single daily application was found to be effective in the treatment of the most common causes of vaginitis. (c) 2008 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Advantages and Pitfalls of the Polymerase Chain Reaction in the Diagnosis of Esophageal Ulcers in AIDS Patients

HIV-1-infected patients frequently have opportunistic esophageal infections which, when associated with severe immunodeficiency, can be attributed to unusual pathogens. The clinical presentation of several esophageal diseases is similar and the best method for a specific diagnosis of these patients has not been well defined. To evaluate the role of the polymerase chain reaction (PCR) in the etiologic definition of esophageal ulcers in HIV-1-infected patients, 96 esophageal biopsies from 79 HIV-1-infected patients were processed by PCR using specific primers for cytomegalovirus (CMV), herpes virus (HSV), human papilloma virus (HPV), HIV-1, Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium intracellulare, Treponema pallidum, and Haemophilus ducreyi. The PCR results were compared to the histopathologic results. Seventy-nine patients were studied (mean age: 34 years; 62% men; median CD4 + T cell = 103.59 cells/mu l (range 1-795.2 cells/mu l). The most common endoscopic findings were as follows: esophageal candidiasis (37.1%), esophageal ulcers (24.7%), esophagitis (11.2%), and lugol-negative areas (10.1%). The histopathologic findings in the esophageal ulcers (22 biopsies) were non-specific inflammation (31.8%), HSV (36.4%), Candida (13.6%), CMV (13.6%), or HPV disease (4.5%). In the esophageal ulcer biopsies, the PCR results were negative in 27.6% of cases, and positive for HIV (65.5%), CMV (31%), HPV (20.7%), HSV (10.3%), and H. ducreyi (6.9%). The histopathologic examination did not identify a pathogen or identified only Candida in 15 biopsies of esophageal ulcers. PCR was positive in ten (66.7%) and negative in five (33.3%) of these biopsies (idiopathic ulcers). PCR detected: HIV (53.3%), CMV (20%), HPV (13.3%), and H. ducreyi (6,7%). PCR detected more etiologic agents in esophageal ulcers than histopathology and was able to detect unusual pathogens. On the other hand, sometimes more than one pathogen was detected in the esophageal ulcers, making it difficult to reach an accurate diagnosis. This finding indicates the need for more studies to evaluate the benefit of this method in the routine evaluation of esophageal ulcer biopsies in HIV-1-infected patients.

Degeneration of dystrophic or injured skeletal muscles induces high expression of Galectin-1

Muscle degenerative diseases such as Duchenne Muscular Dystrophy are incurable and treatment options are still restrained. Understanding the mechanisms and factors responsible for muscle degeneration and regeneration will facilitate the development of novel therapeutics. Several recent studies have demonstrated that Galectin-1 (Gal-1), a carbohydrate-binding protein, induces myoblast differentiation and fusion in vitro, suggesting a potential role for this mammalian lectin in muscle regenerative processes in vivo. However, the expression and localization of Gal-1 in vivo during muscle injury and repair are unclear. We report the expression and localization of Gal-1 during degenerative-regenerative processes in vivo using two models of muscular dystrophy and muscle injury. Gal-1 expression increased significantly during muscle degeneration in the murine mdx and in the canine Golden Retriever Muscular Dystrophy animal models. Compulsory exercise of mdx mouse, which intensifies degeneration, also resulted in sustained Gal-1 levels. Furthermore, muscle injury of wild-type C57BL/6 mice, induced by BaCl(2) treatment, also resulted in a marked increase in Gal-1 levels. Increased Gal-1 levels appeared to localize both inside and outside the muscle fibers with significant extracellular Gal-1 colocalized with infiltrating CD45(+) leukocytes. By contrast, regenerating muscle tissue showed a marked decrease in Gal-1 to baseline levels. These results demonstrate significant regulation of Gal-1 expression in vivo and suggest a potential role for Gal-1 in muscle homeostasis and repair.

Drosophila melanogaster lipins are tissue-regulated and developmentally regulated and present specific subcellular distributions

Lipins constitute a novel family of Mg2+-dependent phosphatidate phosphatases that catalyze the dephosphorylation of phosphatidic acid to yield diacylglycerol, an important intermediate in lipid metabolism and cell signaling. Whereas a single lipin is detected in less complex organisms, in mammals there are distinct lipin isoforms and paralogs that are differentially expressed among tissues. Compatible with organism tissue complexity, we show that the single Drosophila Lpin1 ortholog (CG8709, here named DmLpin) expresses at least three isoforms (DmLpinA, DmLpinK and DmLpinJ) in a temporal and spatially regulated manner. The highest levels of lipin in the fat body, where DmLpinA and DmLpinK are expressed, correlate with the highest levels of triacylglycerol (TAG) measured in this tissue. DmLpinK is the most abundant isoform in the central nervous system, where TAG levels are significantly lower than in the fat body. In the testis, where TAG levels are even lower, DmLpinJ is the predominant isoform. Together, these data suggest that DmLpinA might be the isoform that is mainly involved in TAG production, and that DmLpinK and DmLpinJ could perform other cellular functions. In addition, we demonstrate by immunofluorescence that lipins are most strongly labeled in the perinuclear region of the fat body and ventral ganglion cells. In visceral muscles of the larval midgut and adult testis, lipins present a sarcomeric distribution. In the ovary chamber, the lipin signal is concentrated in the internal rim of the ring canal. These specific subcellular localizations of the Drosophila lipins provide the basis for future investigations on putative novel cellular functions of this protein family.

Oral lesions and immune reconstitution syndrome in HIV+/AIDS patients receiving highly active antiretroviral therapy. Epidemiological evidence

Objective: To determine whether opportunistic oral infections associated to HIV infection (OOI-HIV) are found in HIV+/AIDS patients with immune reconstitution related to highly active antiretroviral therapy (HAART). Methods. From among 1100 HIV+/AIDS patients (Service of Internal Medicine, Carlos Haya Hospital, Malaga, Spain) subjected to review of the oral cavity between January 1996 and May 2007, we identified those examined in 1996 and which were again examined between 1997 and 2007, and were moreover receiving HAART. The following data were collected: age, gender, form of contagion, antiretroviral therapy at the time of review, number of CD4+ lymphocytes/ml, and viral load (from 1997 onwards). We identified those subjects with an increase in CD4+ lymphocytes/ ml associated to HAART, and classified them as subjects with quantitative evidence of immune reconstitution (QEIR). Among these individuals with QEIR we moreover identified those with undetectable viral loads (QEIR+VL), and differentiated those patients with an increase in CD4+ lymphocytes > 500/ml (QEIRm+VL). In each group we determined the prevalence of OOI-HIV, following the diagnostic recommendations of the EC-Clearinghouse (CDC-Atlanta, USA - WHO). In addition, we analyzed the prevalence of OOI-HIV in the different groups in relation to the duration of HAART. Results. A total of 86 subjects were included (44 females and 42 males; 19 heterosexuals, 34 male homosexuals, and 33 intravenous drug abusers). Forty-two patients showed QEIR: 21 belonged to the QEIR+VL group, and 17 conformed the QEIRm+VL group. The prevalence of OOI-HIV per group was as follows: QEIR = 54.8%; QEIR+VL = 33%; QEIRm+VL = 35%. The most prevalent lesion in all groups was erythematous candidiasis. OOI-HIV increased with the duration of HAART (p=0.008), and were seen to be dependent upon late appearance of the mycotic lesions ( after 24 months under HAART). Conclusions: It is suggested that opportunistic oral infections associated to HIV infection form part of the clinical picture of immune reconstitution inflammatory syndrome, though such infections are of late onset.

Oral manifestations of human T-cell lymphotropic virus infection in adult patients from Brazil

Objective: Human T-cell lymphotropic virus type 1 (HTLV-1) was the first human retrovirus discovered and its pathogenesis is related to T cells infection. This study aimed to verify the presence of oral manifestations in a Brazilian population of patients who was seropositive for HTLV, and identify risk factors for oral manifestations. Subjects and methods: An assessment was made of 139 patients at the Emilio Ribas Institute of Infectious Diseases. Results: A total of 112 (80.5%) patients were HTLV-1, 26 (18.7%) were HTLV-2+. About 35.2% of patients had myelopathy/tropical spastic paraparesis (HAM/TSP), with 48 of them being HTLV-1+ and one patient was seropositive for HTLV-1 and -2. The most common oral manifestations were: xerostomia (26.8%), candidiasis (20.8%), fissured tongue (17.9%), and loss of tongue papillae (10.0%). A multivariate logistic regression analysis showed that HAM/TSP is an independent risk factor for xerostomia (P = 0.02). The patients who were HAM/TSP+ were three times more likely to develop xerostomia when compared with patients without HAM/TSP (odds ratio = 2.69, 95% confidence interval = 1.17-6.17). Conclusion: Despite the fact that the findings of this study suggest a relationship between xerostomia and HAM/TSP, more studies should be developed to show what the association would be between xerostomia presented by HTLV patients and pathogenesis of the virus.

Oral status and Candida colonization in patients with Sjogren`s Syndrome

Objective: To determine the oral status, salivary flow rate, Candida carriage in saliva, and prevalence of Candida albicans colonization in several areas of the mouth in patients with primary and secondary Sjogren`s syndrome as opposed to those of healthy subjects. Study design: Thirty-seven patients with Sjogren`s syndrome (SS), [14 patients with primary SS (SS-1) and 23 patients with secondary SS (SS-2)], along with 37 healthy controls were examined in regard to number of teeth, pro-bing pocket depth (PPD), approximal plaque index (API), bleeding on probing (BOP), presence of prosthetic appliances and smoking habits. Salivary flow rate (SFR), Candida carriage in saliva, presence of Candida albicans colonization on buccal, angular, palatal and sulcular areas, on dentures and on the tongue`s dorsal surface were determined. Statistical analyses were performed using the 2-tailed Fisher exact and Kruskal-Wallis test. Results: No statistically significant difference was found between SS-1 and SS-2 groups based on the parameters analysed. Statistically significant differences were observed between patients with SS and healthy subjects in terms of SFR, oral signs and symptoms, API, BOP, C. albicans colonization on tongue and buccal area, and Candida carriage in saliva. In the gingival crevicular fluid positive C. albicans colonization was found in only one subject of SS subgroup. Conclusions: SS patients carry a higher risk of having periodontitis and are more predisposed to develop candidiasis. C. albicans is scarcely detected in gingival crevicular fluid despite high scores on C. albicans colonization in different areas of the oral cavity in SS patients.

Herpes viruses in periodontal compromised sites: comparison between HIV-positive and -negative patients

Aims: The objective of this study was to compare the frequency of herpes simplex virus type 1 (HSV-1), Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) in subgingival plaque, saliva and peripheral blood of HIV-positive and-negative patients with periodontal disease. Materials and Methods: Fifty HIV-positive subjects (23 with gingivitis, 27 with periodontitis) and 50 healthy HIV-negative patients with chronic periodontitis were included in the study. Parameters of probing depth (PD), clinical attachment level (CAL), gingival index and plaque index were recorded. The samples were processed for viral identification by the nested polymerase chain reaction technique. Results: HCMV was the most prevalent virus in HIV-positive (82%) and-negative patients (84%), and the detection in the three samples was similar (p > 0.05). HSV-1 was the least prevalent virus in both groups, being detected in similar frequencies in oral sites and in peripheral blood. EBV-1 was found more frequently in saliva and subgingival plaque of HIV-positive patients than in HIV-negative patients (p <= 0.05). Conclusions: EBV-1 was more frequently recovered in oral sites of HIV-positive patients than in HIV-negative patients.

Impact of PI and NNRTI HAART-based therapy on oral lesions of Brazilian HIV-infected patients

Background: The incidence of oral lesions related to human immunodeficiency virus (HIV) infection have been investigated after treatment with highly active antiretroviral therapy (HAART) including protease inhibitors (PI) but no data are available on the effect of non-nucleoside reverse transcriptase inhibitor (NNRTI)-based therapy on incidence of acquired immunodeficiency syndrome (AIDS) oral manifestations or impact of HAART on oral manifestations of HIV infection in Brazil. The aim of this study was to describe the effects of anti-HIV therapy on the incidence of oral lesions during 17 years of AIDS epidemics in a Brazilian population. Methods: From 1989 to 2006, we collected data from 1595 consecutive HIV patients at the Special Care Dentistry Center, Sao Paulo, Brazil. We compared the effect of PI- and NNRTI-based antiretroviral therapy (ARVT) on the annual incidence of Kaposi sarcoma (KS), oral candidiasis (OC) and hairy leukoplakia (HL). The chi-squared test was used to test the association between oral lesions and therapeutic regimen (P < 0.05). Results: None of patients on ARVT presented with KS. Patients who used (nucleoside reverse transcriptase inhibitors) NRTI + PI were 0.9 times as likely to present with HL as those who used NRTI + NNRTI. This finding, however, was not statistically significant (P = 0.5). The relative risk for OC was 0.8 in patients with PI-based HAART. The increased risk among those on PIs was statistically significant (P = 0.004). Conclusions: The superiority of NNRTI regimens in decreasing OC incidence is consistent with current therapeutic guidelines which recommend NNRTI-based therapy as the treatment of choice for initial ARVT.

Oral manifestations after immune reconstitution in HIV patients on HAART

In order to verify possible association between immune reconstitution inflammatory syndrome (IRIS) and oral manifestations (OMs), we selected AIDS patients who had low CD4 count before the initiation of highly active antiretroviral therapy (HAART) and who returned three months later for therapy evaluation. The oral lesions observed three months after the initiation of HAART were evaluated and associated with the type of antiretroviral therapy (ART), CD4 count and HIV-RNA load levels (before and three months after HAART initiation). A total of 105 patients matched the selected criteria. Immune reconstitution (IR) was identified in 35.2%. Among these patients, the mean CD4 cell count rose from 105.97 to 330.29 and the mean viral load dropped from 168.005 (log 5.22) to 21.852 (log 4.33). There was no significant difference in age (P=0.78), sex (P=0.41) or previous history of ART (P=0.55) between IR and non-IR patients. In the IR group, the most common OM was. parotid enlargement (57.14%) (P=0.619), whereas in the non-IR group candidiasis (46.15%) was the most common OM. The results of our study suggest that the parotid gland enlargement found in the studied population might be an IRIS event, as it was found in patients with IR three months after the initiation of HAART.

Protein targeting to the plasma membrane of adult skeletal muscle fiber: An organized mosaic of functional domains

The plasma membrane of differentiated skeletal muscle fibers comprises the sarcolemma, the transverse (T) tubule network, and the neuromuscular and muscle-tendon junctions. We analyzed the organization of these domains in relation to defined surface markers, beta -dystroglycan, dystrophin, and caveolin-3, These markers were shown to exhibit highly organized arrays along the length of the fiber. Caveolin-3 and beta -dystroglycan/dystrophin showed distinct, but to some extent overlapping, labeling patterns and both markers left transverse tubule openings clear. This labeling pattern revealed microdomains over the entire plasma membrane with the exception of the neuromuscular and muscle-tendon junctions which formed distinct demarcated macrodomains. Our results suggest that the entire plasma membrane of mature muscle comprises a mosaic of T tubule domains together with sareolemmal caveolae and beta -dystroglycan domains. The domains identified with these markers were examined with respect to targeting of viral proteins and other expressed domain-specific markers, We found that each marker protein was targeted to distinct microdomains, The macrodomains were intensely labeled with all our markers. Replacing the cytoplasmic tail of the vesicular stomatitis virus glycoprotein with that of CD4 resulted in retargeting from one domain to another. The domain-specific protein distribution at the muscle cell surface may be generated by targeting pathways requiring specific sorting information but this trafficking is different from the conventional apical-basolateral division. (C) 2001 Academic Press.

Urine D-arabinitol/L-arabinitol ratio in diagnosing Candida infection in patients with haematological malignancy and HIV infection

Adult patients with hematologic malignancies along with HIV infected patients were prospectively studied to determine the performance of urine D-arabinitol/L-arabinitol (DA/LA) ratio in diagnosing invasive candidiasis. Ten evaluable febrile neutropenic patients had proven invasive candidiasis and elevated DA/LA ratios were found in 5. Invasive candidiasis with normal DA/LA ratios was most frequently due to Candida krusei infection. This Candida species is a non-producer of arabinitol. Only 4 of 81 febrile neutropenic patients given either antifungal prophylaxis or empiric antifungal treatment had elevated DA/LA ratios. Only 1 of 15 HIV positive patients with either oropharyngeal or esophageal candidiasis had elevated DA/LA ratios. Widespread use of fluconazole prophylaxis in bone marrow transplantation patients at the study hospital has led to an increased prevalence of C. krusei infection. This is the likely reason for the low sensitivity of the test in proven and suspected invasive Candida infections reported here. (C) 2002 Elsevier Science Inc. All rights reserved.

Mutations in the human ortholog of Aristaless cause X-linked mental retardation and epilepsy

Mental retardation and epilepsy often occur together. They are both heterogeneous conditions with acquired and genetic causes. Where causes are primarily genetic, major advances have been made in unraveling their molecular basis. The human X chromosome alone is estimated to harbor more than 100 genes that, when mutated, cause mental retardation(1). At least eight autosomal genes involved in idiopathic epilepsy have been identified(2), and many more have been implicated in conditions where epilepsy is a feature. We have identified mutations in an X chromosome-linked, Aristaless-related, homeobox gene (ARX), in nine families with mental retardation (syndromic and nonspecific), various forms of epilepsy, including infantile spasms and myoclonic seizures, and dystonia. Two recurrent mutations, present in seven families, result in expansion of polyalanine tracts of the ARX protein. These probably cause protein aggregation, similar to other polyalanine(3) and polyglutamine(4) disorders. In addition, we have identified a missense mutation within the ARX homeodomain and a truncation mutation. Thus, it would seem that mutation of ARX is a major contributor to X-linked mental retardation and epilepsy.