Systematic truncations of chromosome 4 and their responses to antifungals in Candida albicans.

BACKGROUND: Candida albicans is an opportunistic human fungal pathogen responsible for superficial and systemic life-threatening infections. Treating these infections is challenging as many clinical isolates show increased drug resistance to antifungals. Chromosome (Chr) 4 monosomy was implicated in a fluconazole-resistant mutant. However, exposure to fluconazole adversely affects Candida cells and can generate numerous mutations. Hence, the present study aimed to truncate Chr4 and challenge the generated Candida strains to antifungals and evaluate their role in drug response. RESULTS: Herein, Chr4 was truncated in C. albicans using the telomere-mediated chromosomal truncation method. The resulting eight Candida strains carrying one truncated homolog of Chr4 were tested for response to multiple antifungals. The minimal inhibitory concentration (MIC) for these strains was determined against three classes of antifungals. The MIC values against fluconazole, amphotericin B, and caspofungin were closer to that of the wild type strain. Microdilution assay against fluconazole showed that the mutants and wild type strains had similar sensitivity to fluconazole. The disc diffusion assay against five azoles and two polyenes revealed that the zones of inhibition for all the eight strains were similar to those of the wild type. Thus, none of the generated strains showed any significant resistance to the tested antifungals. However, spot assay exhibited a reasonably high tolerance of a few generated strains with increasing concentrations of fluconazole. CONCLUSION: This analysis suggested that Chr4 aneuploidy might not underlie drug resistance but rather drug tolerance in Candida albicans.

Mechanism of streptomyces albidoflavus STV1572a derived 1-heneicosanol as an inhibitor against squalene epoxidase of Trichophyton mentagrophytes.

An increase in incidences of tinea infections paves the way to discover the novel antifungal drugs from unexplored natural resources. The quality of life in patients with tinea infection may be affected by different factors, including morbidity, length of illness, social and demographic factors. The present investigation explores the functional principle of a bioactive compound isolated from actinomycetes, S. albidoflavus STV1572a by in-silico and in-vitro studies. In continuation of our previous reports on the antidermatophytic potential of S. albidoflavus STV1572a, this study progresses with the in-silico molecular docking study of the seven GC-MS discovered ligands, and six dermatophytic modelled targets. Through virtual screening, it was revealed that a docking score -8.8 between 1-heneicosanol and squalene epoxidase favored partially in understanding the mode of action. Further validation of in-silico study was performed by a sterol quantification assay which confirmed the antidermatophytic mechanism of 1-heneicosanol. Taken together, the evidence from this study suggests that 1-heneicosanol has a potential antidermatophytic compound and can be considered for dermatophytic treatment.

Design, expression, and evaluation of novel multiepitope chimeric antigen of Wuchereria bancrofti for the diagnosis of lymphatic filariasis - A structure-based strategy.

The Global Program for Elimination Lymphatic Filariasis (GPELF) is in an advanced stage and requires tools for diagnosing infection, assessing transmission and certification. This study was aimed at developing an antibody-based assay using a chiemric antigen containing multi-B-cell epitopes from antigens highly expressed in different stages of Wuchereria bancrofti to detect LF infection and its transmission. The antigen was express cloned and two indirect ELISA based (IgG1 & IgG4 based) antibody assays were developed using the recombinant antigen. The chimeric antigen displayed 1 and 3-fold reactivity with IgG1 and IgG4 antibodies, respectively in microfilaraial (mf) positive sera when compared to that in sera samples of Non-endemic normal sera (NEN) (O.D, 0.13 ± 0.20 and 0.18 ± 0.07), thus differentiating infected from uninfected individuals. In IgG1 and IgG4 antibody assays, the multiepitope antigen also showed reactivity (O.D, 0.27 ± 0.18 and 0.16 ± 0.03) in a small proportion (18 and 30, respectively out of 156) endemic normal individuals and in IgG1 antibody in a few (4) chronic patients (CP). The antigen did not react with IgG1 or IgG4 antibodies in the sera samples of malaria, scrub typhus, dengue, hookworm, and roundworm helminth cases (0.139 ± 0.018, 0.144 ± 0.007 0.17804 ± 0.007 and 0.162 ± 0.006), thus showing its high specificity. The sensitivity (%) and specificity (%) of the multi-epitope antigen-based IgG1 and IgG4 antibody assays are 100, 98.1 and 100, 99.52, respectively. Thus, the recombinant multiepitope antigen appears to have good potential in detecting active LF infection and in assessing its transmission in endemic communities.

Structural, molecular, functional and immunological characterization of Wuchereria bancrofti-galectin.

Galectins regulate growth and differentiation of immune cells and inflammation through their carbohydrate-binding function in humans, while also play a role in parasite survival. This study focused on the galectin of lymphatic filarial parasite Wuchereria bancrofti (Wb-Gal). The multiple sequence alignment with other galectins showed that the Wb-Gal belonged to galactoside binding lectin family, particularly tandem repeat type galectin-9. A homology model of Wb-Gal was developed in the I-TASser server using high similarity 3D structures with a quality score of 89.5. Molecular docking and dynamics studies revealed that the CCRD and NCRD of Wb-Gal bind with galactose and lactose. Further, Wb-Gal was cloned into the pET28 vector, expressed in E. coli Rosetta strain and purified by affinity chromatography. In the hemagglutination assays, the rWb-Gal bound to lactose, galactose, and glucose. Indirect Enzyme-Linked Immunosorbent Assay (ELISA) using different clinical filarial sera showed that the IgG and IgM response was against Wb-Gal x very high in all filarial clinical groups, whereas the IgA and IgG2 response was minimum to negligible. There was an enhanced response of IgG1 and IgG4 antibodies in Microfilaremics (MF) cases compared to Chronic Pathology (CP) and Endemic Normal (EN) individuals. Interestingly, the IgE response was comparatively higher in EN than MF and CP. These studies show that Wb-Gal is a member of the lectin family of proteins binding to different carbohydrates and may have an important role in the pathophysiology of filarial infection which needs to be investigated in greater detail.

Scleral Buckling and Corneal Topography in a Rare Case of Keratoconus with Rhegmatogenous Retinal Detachment in an Indian Patient.

BACKGROUND: Management of Rhegmatogenous Retinal Detachment (RRD) in keratoconus could be challenging in various aspects. Visualisation of fundus due to altered reflex along with axial myopia could pose difficulty while performing pars plana vitrectomy. Our patient underwent Scleral Buckling with good anatomical results. We came across an isolated case of Keratoconus with Retinal detachment without any pre existing comorbidities unlike earlier reports where patients with history of atopic dermatitis had Keratoconus associated with RRD. The main purpose was to know the outcome of scleral buckling and its effect on corneal topography in a case of keratoconus with RRD. CASE: A 35 year old female presented with diminution of vision in both eyes since childhood, but more so in the right eye (RE) since last 6 months. She was aphakic with VA of 1/60 and 2/60 in the right and left eye respectively. She was diagnosed as both eyes keratoconus with RE near total rhegmatogenous retinal detachment (RRD) with sub retinal gliosis. She gave no history of vigorous eye rubbing or atopic dermatitis. For RE she underwent uneventful scleral buckling surgery. OBSERVATION: In post operative follow up, the retina was attached. Placido based corneal topography was done pre operatively with keratometry reading of RE - K1 62.79@96º, K2 - 55.92@6˚ and repeated at the end of three months follow up with readings of RE - K1-61.45@98˚, K2- 54.50@ 8˚. There were minimal changes in the keratometry values post operatively with flattening of vertical meridian and horizontal meridian. CONCLUSION: In keratoconus, RD can occur without any predisposed or preceding condition. Although majority of cases are associated with atopic dermatitis and eye rubbing. Scleral buckling (SB) was successful with good functional and anatomical outcome., however it has minimal effect on corneal topography.

Assessment of age of majority by measurement of open apices of the third molars using Cameriere's third molar maturity index.

AIMS AND OBJECTIVES: Evaluation of biological age of a living subject around the legal cutoff age for adulthood has become a grave concern for forensic experts in India, mainly due to the consequences of criminal obligations in judicial proceedings. Thus, this study was planned to examine the open apices of third molars in discriminating between individuals who are aged 18 years or older and who are not 18 years or older and to assign a cutoff for estimation of the age of 18 years. MATERIALS AND METHODS: Orthopantomographs of 1062 individuals (14 and 23 years) were assessed, to verify Cameriere's third molar maturity index (I3M). The apical ends of the roots of the left mandibular third molar were analyzed. If the apical ends of the roots are completely closed, then I3Mis zero; otherwise, it is calculated as the sum of the distances between the inner sides of the two open apices divided by the tooth length. RESULTS AND CONCLUSION: The sensitivity of the test for 0.08 value was 74.7% for males and 66% for females. Specificity was 83.6% for males and 79.6% for females. The probability that an Indian individual with an I3M<0.08 in 18 years or older is 78% for males and 70.3% for females. I3Mis efficacious to determine age in Indian population.

Inflammatory linear verrucous epidermal nevus and regional odontodysplasia: A rare sorority.

Epidermal nevi are hamartomatous lesion and its association with other developmental defects particularly of the central nervous system, eye and skeletal system are well recognized. We report a rare case of inflammatory linear verrucous epidermal nevus syndrome along with regional odontodysplasia; and to the best of our knowledge this is the second case reported in the literature.

2-(1H-Benzimidazol-2-yl)phenol.

The title mol-ecule, C13H10N2O, is essentially planar, the maximum deviation from the plane of the non-H atoms being 0.016 (2) Å. The imidazole ring makes a dihedral angle of 0.37 (13)° with the attached benzene ring. An intra-molecular O-H⋯N hydrogen bond generates an S(6) ring motif. In the crystal, mol-ecules are linked through N-H⋯O hydrogen bonds, forming chains propagating in [001]. The crystal packing also features four π-π stacking inter-actions involving the imidazole ring, fused benzene ring and attached benzene ring system [centroid-centroid distances = 3.6106 (17), 3.6108 (17), 3.6666 (17) and 3.6668 (17) Å].

2-(Naphthalen-1-yl)-1-phenyl-1H-benzimid-azole benzene hemisolvate.

In the title compound, C23H16N2·0.5C6H6, the benzimidazole unit [maximum deviation = 0.0258 (6) Å] and the naphthalene ring system [maximum deviation = 0.0254 (6) Å] are both essentially planar and make a dihedral angle of 61.955 (17)°. The imidazole ring makes dihedral angle of 61.73 (4)° with the phenyl ring. An intra-molecular C-H⋯N hydrogen bond generates an S(6) ring motif. In the crystal, seven weak C-H⋯π inter-actions involving the fused ring system, the benzene solvent mol-ecule, the imidazole phenyl rings are observed, leading to a three-dimensional architecture.

Morphometric evaluation of soft palate in oral submucous fibrosis--a digital cephalometric study.

The Present study was carried out to evaluate the morphology of soft palate in Oral Submucous Fibrosis (OSF) patients using digital lateral cephalogram. A total number of 70 patients were included in the study (Control group had 35 patients and Study group had 35 OSF patients) were evaluated for soft palate by digital lateral cephalogram. The anterio-posterior length and superior-inferior length of soft palate were measured. The morphology of soft palate was categorized as type 1, to type 6. Different types of soft palate were compared with stages of OSF. Among the Study group (35 patients) 62.9% had Stage 2 OSF. Leaf shaped (Type 1) soft palate was seen commonly in stage 2 OSF whereas butt shaped (Type 3) in stage 3 OSF. In the present study there was statistically significant difference in length (anterio-posterior) of Type 1 soft palate of OSF patients. In the present study as the OSF progressed to advanced stage there was gradual change from Type 1 and Type 2 variety of Soft palate to Type 3 and Type 6 variety of soft palate. The study observed that there was gradual reduction in the length of soft palate in anterior-posterior direction in OSF patients.

Oral manifestations of lipoid proteinosis: A case report and literature review.

Lipoid proteinosis is an uncommon autosomal recessive metabolic disorder that presents in early life with hoarseness and pox-like acneiform scars involving the skin and mucous membranes. Previous studies have attributed the prevalence of lipoid proteinosis to consanguineous parents. This paper reports a classical case of lipoid proteinosis with oral manifestations but without a history of consanguinity.

Multiple gingival metastasis of adenocarcinoma of the lung.

Metastasis to the gingival soft tissues is an extremely rare phenomenon, and metastasis of multiple lesions (i.e. more than 2 lesions), is even more hard to find. In this study, we have reported a rare case of lung adenocarcinoma, which metastasized to the maxillary (2 lesions) and mandibular gingivae (1 lesion) in a 57 year old male patient. Metastasis was also seen to the vertebrae. The differential diagnosis consisted of acute myelomonocytic leukemia, chronic lymphocytic leukemia, haemangioma, pyogenic granuloma, giant cell granuloma, peripheral fibroma, primary gingival carcinoma and secondary metastasis. Contrast enhanced computed tomography of the lung showed a well-defined mass situated below the right hilum with lower lobe consolidation and pleural effusion on the right side with dorsal spinal metastasis. Excisional biopsy of the lesions was consistent with the diagnosis, and the immunohistochemical analysis was positive for cytokeratin 7, carcinoembryonic antigen (CEA), thyroid transforming factor 1 (TTF1), and negative for vimentin and cytokeratin 20 (CK20).

Cowden syndrome.

Cowden syndrome or multiple hamartoma syndrome is an autosomal dominant condition with variable expressions that result mainly from mutation in the PTEN gene on arm 10q. It is characterized by multiple hamartomatous neoplasms of the skin, oral mucosa, gastrointestinal tract, bones, CNS, eyes, and genitourinary tract. Mucocutaneous features include trichilemmomas, oral mucosal papillomatosis, acral keratosis, and palmoplantar keratosis. Here we present a case of Cowden syndrome in a 14-year-old female patient with the chief complaint of multiple oral papillomatous lesions.

Blue rubber bleb nevus syndrome: prominent oral findings.

Blue rubber bleb nevus syndrome is a rare disorder characterized by multiple cutaneous venous malformations in association with visceral lesions, most commonly affecting the gastrointestinal tract. Oral cavity lesions occur in 59 to 64% of cases. We report a unique presentation of this syndrome in a 25-year-old male patient with prominent oral findings. This is a sporadic case, started during early childhood, progressively increasing in number and size. Oral vascular lesions were part of gastrointestinal involvement. Associated cardiac abnormalities were also observed. An early diagnosis of this syndrome is required as it gets complicated with bleeding, anemia and other systemic complications.

Effect of Cr in irrigation water on germination and growth of French beans (Dolichos lablab L.).

The waters containing chromium (Cr) mainly from industries enter into the sewers, municipal treatment plant, streams and lakes that are used for irrigation purposes. The effect of Cr in irrigation water on seed germination and growth of French bean (Dolichos lablab L.) was investigated. Germination studies were conducted in the lab and field conditions. Seeds were treated with different concentrations (0 to 25 mg/1) of Cr in irrigation water. The percentage germination of seeds and plant growth showed a gradual decrease with increase in Cr concentration. Stimulatory effect in growth of plant was observed at lower concentration (1 to 2 mg/l). Accumulation of Cr was in the order of Root > Leaf > Stem > Pod. There was an increase in the total concentration of Cr content of soil with increase in Cr concentration in irrigation water.