Clinical Profile of Patients with Leber Hereditary Optic Neuropathy (LHON): An Ambispective Study of North Indian Cohorts.

Background: Leber hereditary optic neuropathy (LHON) is a maternally inherited disease resulting in irreversible visual loss usually in patients belonging to the age group of 15-35 years. Clinically, the patients present with sequential or bilateral, painless, progressive visual loss with central (or ceco-central) scotomas. Although the three mutations, namely, G11778A, T14484C, and G3460A contribute to >95% of LHON cases globally, the relative frequency of each mutation varies. Aims and Objectives: We aimed to assess the clinical and genetic profile of patients with mutation-positive LHON at a north Indian tertiary care center. Materials and Methodology: One hundred sixty-one patients (61 prospective and 100 retrospective) presenting with the clinical diagnosis of LHON were screened for the three known mitochondrial mutations (G1178A, G3460A, T14448C). Patients were assessed for detailed clinical, ophthalmological, and neurological examinations. Five milliliter of blood sample was taken to assess the three known mutations using DNA isolation and Sanger sequencing. Results and Discussion: Clinical profile of 83 patients with both positive and negative mutations was analyzed. Twenty-three out of 161 patients (14.3%) tested positive for either of the three mutations. The majority of the patients harbored G11778A mutation (56.52%) followed by T14484C (34.78%) and G3460A (8.69%). No statistical difference could be noted between the clinical profiles of mutation-negative and -positive patients.

Role of Orthoboon (glucosamine sulfate + collagen + Vitamin C): A novel host-modulating agent in the management of chronic periodontitis.

BACKGROUND: Recent trends suggest using novel host-modulating agents as a treatment strategy for chronic periodontitis. Glucosamine sulfate (GS) was proven to have anti-inflammatory actions related to its ability to suppress neutrophil functions. Orthoboon, an anti-arthritic and anti-inflammatory drug, has shown to have a positive therapeutic effect due to its constituents made of a combination of GS, Vitamin C, and collagen. The aim of the study was to evaluate the host modulatory effects of Orthoboon on periodontal status and to estimate the C reactive protein (CRP) levels before and after nonsurgical periodontal therapy (NSPT). MATERIALS AND METHODS: A total number of 40 patients with chronic periodontitis were randomly divided into two groups of 20 patients each. The test group patients (n = 20) received 500 mg Orthoboon three times daily for 45 days. Prior to the initiation of Orthoboon, all patients in both test group and control group were subjected to Phase I periodontal therapy. CRP levels were estimated immediately after phase I therapy and 45 days after therapy. Clinical parameters including plaque index, gingival index, and bleeding index were recorded before and after NSPT for the two groups. RESULTS: The mean CRP levels were reduced significantly in the test group before and after administration of Orthoboon and also there were statistically significant differences in the mean CRP levels at the end of 45 days between the test group and the control group. CONCLUSION: Administration of Orthoboon, i.e., GS, with a combination of Vitamin C and collagen was proved to be of a significant benefit in the test group than in the control group.

Mapping the link between cardiac biomarkers and chronic periodontitis: A clinico-biochemical study.

BACKGROUND: Various risk factors are coupled with atherosclerotic complications, such as myocardial infarction and stroke. Periodontitis is considered one of them. AIMS AND OBJECTIVES: The objective of the study is to compare and correlate the occurrences of periodontitis with serum levels of cardiac-biomarkers in patients with coronary heart-disorders. MATERIALS AND METHODS: Of 70 individuals diagnosed with coronary artery diseases, 32 patients with chronic periodontitis constituted the test group, 31 without chronic periodontitis constituted the control group. Cardiac-biomarkers analyzed were Troponin T, Troponin I, Myoglobin; low density lipoprotein (LDL), high-density lipoprotein, very LDL (VLDL), total cholesterol (TC), and highly sensitive C-reactive protein (Hs-CRP). Periodontal characteristics were drawn from the plaque index (PI) and gingival index, probing depth (PD), clinical attachment loss, and periodontal inflammatory surface area (PISA). STATISTICAL ANALYSIS: In order to separate any association between cardiac biomarkers and clinical parameters of periodontitis, detailed statistical analysis through independent t-test and Pearson test of correlation was done. RESULTS: Statistically significant differences were seen not only in PI, PD, and PISA between both the groups (P < 0.05), but also between various cardiac parameters of test and control groups (P < 0.001). Positive relations were seen in the test group, between cardiac biomarkers such as TC, VLDL, Hs-CRP, and Troponin T with periodontal parameters such as PD and PISA. CONCLUSION: The study reveals, a strong association between periodontitis and diseases of cardiovascular nature, highlighting the need for awareness and timely medical interventions to prevent periodontitis from scaling up and interfering with the risk of cardiovascular problems.

Evaluation of Serum Leptin and Adiponectin in Obese Individuals with Chronic Periodontitis.

OBJECTIVES: Studies have reported changes in leptin and adiponectin levels in the gingival crevicular fluid, saliva, and blood serum of obese patients with periodontal disease. The aim of the study is to evaluate serum leptin and adiponectin levels in obese and nonobese individuals with chronic periodontitis and to deduce a relationship between the clinical parameters and the inflammatory biochemical parameters. MATERIALS AND METHODS: In this case-control study, a total of fifty individuals were selected based on the body mass index (BMI): Group I of obese individuals with chronic periodontitis and Group II of nonobese individuals with chronic periodontitis. Periodontal parameters used in this study were plaque index, gingival index, probing pocket depth, and clinical attachment level. The effects of obesity and periodontal status on serum leptin and adiponectin levels of both groups were statistically analyzed using an independent t- test. RESULTS: Statistical analysis showed that the effect of BMI on serum leptin and adiponectin levels was statistically significant (P < 0.01), and the effect of chronic periodontitis on the serum leptin and adiponectin levels was also statistically significant compared to nonobese individuals (P < 0.0001). However, there is no statistically significant correlation between serum leptin and adiponectin, which indicates that both are independent to each other. CONCLUSIONS: In obese individuals with chronic periodontitis, serum leptin levels were significantly high compared to nonobese individuals and serum adiponectin levels were significantly lower in obese individuals compared to nonobese individuals with periodontitis, though both the parameters were independent of each other.

Association of pentraxin and high-sensitive C-reactive protein as inflammatory biomarkers in patients with chronic periodontitis and peripheral arterial disease.

CONTEXT: Inflammation is a common feature of both peripheral artery disease (PAD) and periodontal disease. AIM: The aim of this study is to evaluate the relationship between PAD and periodontal disease by examining the levels of inflammatory cytokines, pentraxin-3 (PTX-3), and high-sensitive C-reactive protein from serum. MATERIALS AND METHODS: A total of 50 patients were included in this cross-sectional study. Patients were divided into two groups: those with PAD (test group) and those with the non-PAD group (control group) based on ankle-brachial index values. Periodontal examinations and biochemical analysis for PTX-3 and high-sensitive C-reactive protein were performed to compare the two groups. STATISTICAL ANALYSIS USED: All the obtained data were sent for statistical analyses using SPSS version 18. RESULTS: In the clinical parameters, there is statistically significant difference present between plaque index, clinical attachment loss, and periodontal inflammatory surface area with higher mean values in patients with PAD having periodontitis. There is statistical significant (P < 0.01) difference in all biochemical parameters (P < 0.05) considered in the study between PAD patients and non-PAD patients with higher mean values of total cholesterol (TC), low-density lipoprotein (LDL), high-sensitive C-reactive protein (hs-CRP), and PTX-3. CONCLUSION: PTX-3 and acute-phase cytokine such as hs-CRP can be regarded as one of the best indicators to show the association between the PAD and periodontitis followed by hs-CRP, TC, very LDL (VLDL), and LDL. However, high-density lipoprotein (HDL) is a poor indicator for its association with chronic periodontitis and PAD.

Computational Screening of CCR5 Inhibitors as Potential Entry Inhibitor Microbicides Using 3D-QSAR Studies, Docking and Molecular Dynamics Simulation.

BACKGROUND: The chemokine receptor CCR5 acts as a co-receptor for HIV binding and it is considered as an important target by CCR5 antagonists. Entry inhibitor based microbicides gain much importance nowadays as these drugs act at an early stage of HIV lifecycle and thus hinder the viral replication process in humans. The present study intends to identify a CCR5 antagonist which could be developed as a microbicide using computational approaches. METHODS: The pharmacophore modeling and 3D QSAR studies was used to screen CCR5 antagonists with enhanced antagonist activity. The docking studies ranked the compounds according to their binding affinity and molecular dynamics simulation validated the stability of the enzymeligand complex. RESULTS: A five point pharmacophore hypothesis HHPRR (2 hydrophobic; 1 positively ionisable; 2 aromatic ring) was generated. A statistically significant 3D QSAR model with 3 PLS factors was gen- erated for common pharmacophore hypothesis HHPRR.3 with good correlation coefficient value (R2=0.7483). The docking studies revealed that molecular interaction of CCR5 antagonists having good binding affinity are better than the microbicides taken for this study. The QSAR maps revealed the regions as a combined effect of hydrogen bond donors, hydrogen bond acceptors and hydrophobic groups which denoted the substitution of groups indicating the favorable and unfavorable regions for antagonist activity of hydroxypiperidine derivatives. The docking analysis and molecular dynamics simulation screened and validated CCR5 antagonists. CONCLUSION: The present study was successful in identifying a CCR5 antagonist which could be developed as a microbicide.

Atomic Force Microscopy: A three-dimensional reconstructive tool of oral microbiota in gingivitis and periodontitis.

AIM: This study aims to ascertain the advantages of Atomic Force Microscopy (AFM) in the morphologic study of microorganisms and their interactions within the subgingival biofilm in patients with gingivitis and periodontitis. SETTINGS AND DESIGN: Conducted a study on twenty patients, ten patients with severe periodontitis with probing the pocket depth of ≥8 mm, with a clinical attachment loss (CAL) of ≥6 mm CAL and ten patients with gingivitis: ≥5 mm pocket depth, and no attachment loss, was selected for the study. MATERIALS AND METHODS: Bacterial biofilms were collected and slide preparation done. Morphological study was done using AFM. AFM consists of a cantilever-mounted tip, a piezoelectric scanner, a photodetector diode, a laser diode, and a feedback control. The laser beam is reflected from back of the cantilever into the quadrant of the photodetector. AFM works on the principle of interaction between the tip and the sample which causes the cantilever to deflect, thereby changing the position of laser onto the photodetector. Methodology used for studying the bacteria through AFM includes the following: (1) Probe type: Platinum coated silicon nitrate tip. (2) Probe force: 0.11 N/m. (3) Probe geometry: Triangular shaped tip. (4) Probe frequency: 22 KHz. (5) Probe immobilization: Used in Contact mode. AFM Solver Pro-M (NT-MDT) equipped with ETALON probe was used to take images in Nova software. RESULTS: The investigation showed various morphological features, such as shape, size, and secretory product-like vesicles of the bacterial species involved in gingivitis and periodontitis. More bacterial surface details were studied by reproducing a three-dimensional reconstruction using AFM. CONCLUSIONS: The morphological variations of bacteria of different sizes, and shapes, cell wall structures, secretory product-like vesicles flagellated and filamentous microorganisms, polymorphonuclear leukocytes, and bacterial coaggregation analysis were done by AFM. Results of the present study conclude that AFM is a quite a reliable method for studying morphology of bacterial species involving periodontal diseases and is also used to study microbial interactions in biofilm.

Pharmacophore modeling, atom based 3D-QSAR and Molecular docking approaches to screen C-X-C chemokine receptor type 4 antagonists as microbicides for human immunodeficiency virus-1.

The C-X-C chemokine receptor type 4 receptor CXCR4 which acts as a co-receptor for human immunodeficiency virus-1, expressed in the later stages of infection is considered as an attractive and new target for drug design. Microbicides acting as co-receptor blockers are highly significant as these drugs block HIV lifecycle at early stage itself. The urgent need for a safe and effective microbicide urges to explore new CXCR4 antagonists which could be developed as microbicides. The pharmacophore based 3D-QSAR models and docking models were developed using PHASE and GLIDE modules of Schrodinger software. Three-dimensional quantitative structure-activity relationships (3D-QSAR) studies and pharmacophore modelling was carried out on a dataset of 114 CXCR4 antagonists with the intention of exploring entry inhibitors with better therapeutic potential. A training set of 43 compounds was used to create 3D-QSAR models and they were validated using a test set of 28 compounds. CXCR4 antagonists with good inhibitory activity could be designed and structurally modified based upon the QSAR model developed with necessary pharmacophore features. The results revealed that the common pharmacophore hypothesis ADHPR.1 was used for 3D-QSAR model development and the most active compound, CXCR4 antagonist no.44 which is a imidazopyridine-tetrahydro-8-quinolinamine derivative interacted with the CXCR4 receptor residue ASP 97 by the formation of a hydrogen bond. Also, the docking studies were carried out for the dataset for analyzing the binding conformation of CXCR4 and 114 antagonists. The results obtained from the 3D-QSAR studies and docking simulation can be used for designing new and potent CXCR4 antagonists. The compound identified from this study can be taken up further for validation by in vitro/in vivo studies.

Preparation and characterization of biopolymeric nanoparticles used in drug delivery.

Nanotechnology plays an important role in advanced biology and medicine research particularly in the development of potential site-specific delivery systems with lower drug toxicity and greater efficiency. These include microcapsules, liposomes, polymeric microspheres, microemulsions, polymer micelles, hydrogels, solid nanoparticles etc. In the present study, preparation and characterization of biopolymeric gelatin nanoparticles for encapsulating the antimicrobial drug sulfadiazine and its in vivo drug release in phosphate buffer saline (PBS) have been investigated. The nanoparticles prepared by second desolvation process varied in a size range 200 nm and 600 nm with a drug entrapment efficiency of 50% characterized by atomic force microscopy and dynamic light scattering. The drug release from the nanoparticles occurred up to 30% in a controlled manner.

Role of microbicides in the prevention of HIV and sexually transmitted diseases - a review.

Human Immunodeficiency Virus (HIV) leading to the diseased state Acquired Immunodeficiency syndrome (AIDS) and other Sexually Transmitted Diseases caused by various microorganisms are posing a major threat to humankind. Hence there is an urgent need for controlling its spread. In 2008, about 30 million people are living with HIV infection in the world. Heterosexual transmission particularly affecting woman is driving the epidemic today in many resource poor countries, where most of the infections are occurring. One of the biggest potential for prevention for HIV today lies in a method of using a topical microbicide. Microbicides are applied to vaginal or rectal microbicide surfaces with the goal of preventing or at least significantly reducing the transmission of sexually transmitted infections (STI's). This article is presented here as an overview of the various HIV transmission and prevention methods, microbicide development pipeline and other important aspects concerned with it.