Studying the result of underlay myringoplasty using platelet-rich plasma.

OBJECTIVE: Perforations of the tympanic membrane are treated with various surgical techniques and materials. This study aimed to determine the efficacy of platelet-rich plasma during underlay myringoplasty. METHODS: The study included 40 patients. Autologous platelet-rich plasma was applied in-between temporalis fascia graft and tympanic membrane remnant during underlay myringoplasty in group 1 (n = 20). The outcome was evaluated after three months and compared with group 2 (n = 20), a control group that underwent routine underlay tympanoplasty. RESULTS: After three months' follow up, graft uptake was 95 per cent in group 1 and 85 per cent in group 2 (p < 0.03). Mean hearing threshold gain was 18.62 dB in group 1 and 13.15 dB in group 2. This difference was statistically significant (p < 0.01). CONCLUSION: Platelet-rich plasma, with its ease of preparation technique, availability, low cost, autologous nature and good graft uptake rate, justifies its use in tympanoplasty type I procedures.

Role of local application of autologous platelet-rich plasma in the management of pressure ulcers in spinal cord injury patients.

STUDY DESIGN: Prospective clinical case series. OBJECTIVES: The objective of this study is to evaluate the local application of platelet-rich plasma (PRP) in relation to pressure ulcers (PrUs) healing on one PrU (case) versus saline dressing on another PrU (control) in the same patient. SETTING: Tertiary Level Care Centre, India. METHODS: Twenty-five spinal cord injury patients with at least two PrUs were included. All 25 PrUs (case) were grade IV, and PrUs (control) were grade II (n=11), grade IV (n=10) and grade III in 4 patients. Evaluation of PrU healing was done by measuring wound surface area, Pressure Ulcer Scale for Healing (PUSH), biopsy and clinical examination. RESULTS: Statistically significant decrease in mean PUSH scores of PrUs (case) (t=6.13, P<0.000) and PrUs (control) (t=3.98, P=0.000) was observed after 5 weeks. The wound surface area of PrU (case) decreased significantly (t=4.98, P=0.000); however, the decrease was not significant (t=0.095, P=0.924) in PrUs (control). Majority of histopathological pictures of PrUs (case) showed necrosis and suppuration (56%) at the time of enrollment and well-formed granulation tissue and epithelialization (60%) at the 5th week. Twenty-four (96%) PrUs (case) improved and only 1 deteriorated with PRP therapy, whereas in control group 17 (68%) PrUs improved, 7 (28%) deteriorated and 1 wound showed no change. CONCLUSIONS: Advanced wound therapy using local applications of PRP seems to be a promising alternative to standard saline dressings in PrU healing. With the advantages of simple preparation, biocompatible safety, low cost and significant clinical effectiveness, it may be beneficial to study the effects of PRP in large-scale trials to validate it as an ideal therapy for enhanced wound healing in PrUs.

Green chemistry approaches to leather tanning process for making chrome-free leather by unnatural amino acids.

In the present study, green and sustainable method or eco-friendly approaches to tanning process based on unnatural D-amino acids (D-AA)-aldehyde (Ald) as a substitute for chrome-free tanning has been attempted. The distribution of optically active D-AA in tanned leather, the hydrothermal stability, the mechanical properties and resistance to collagenolytic activity of tanned leather, the evaluation of eco-friendly characteristics were investigated. Scanning electron microscopic (SEM) and Atomic force microscopic (AFM) analyses indicate the surface morphology and roughness, respectively, of the tanned leather collagen matrix. Shrinkage and Differential scanning calorimetric (DSC) analyses shows that the shrinkage temperature (T(s)) and denaturation temperature (T(d)) of tanned leather are related to the content of D-AA+Ald present in the leather matrix. It has been found that the T(s) of D-AA tanned leather is more than that of Ald tanned leather and also more or less equal to chrome tanned leather. Environmental impact assessment (EIA) shows that the developed process results in significant reduction in total solids content (TSC) and improves better biodegradability of organic compound present in the effluent compared to chrome tanning.

Comparative evaluation of platelet-rich plasma and guided tissue regeneration membrane in the healing of apicomarginal defects: a clinical study.

INTRODUCTION: The aim of the study was to compare the healing responses of platelet-rich plasma (PRP), PRP + a collagen sponge, and a collagen membrane used as guided tissue regeneration (GTR) materials for the treatment of apicomarginal defects. METHODS: Thirty patients with suppurative chronic apical periodontitis and apicomarginal communication were selected and allocated randomly into three groups according to the barrier technique to be used during periradicular surgery: the collagen membrane group, the PRP group, and the PRP + collagen sponge group. Clinical and radiographic measurements were determined at baseline and every 3 months after surgery up to 1 year. Cases were defined as healed when no clinical signs or symptoms were present, and radiographs showed complete or incomplete (scar tissue) healing of previous radiolucencies. RESULTS: The PRP and PRP + collagen sponge groups depicted 83.33% and 88.89% healing, respectively, in terms of combined clinical-radiographic healing as compared with 80% in the collagen membrane group. All the three treatments showed highly significant (P < .05) reductions in the periodontal pocket depth (PD), the clinical attachment level (CAL), the gingival margin position (GMP), the size of the periapical lesion, the percentage reduction of the periapical rarefactions, and periapical healing. No significant differences between the three groups were evident for these parameters (P > .05). CONCLUSIONS: GTR applied to apicomarginal defects using PRP or PRP + collagen sponge lead to similar enhancements of the clinical outcome of periradicular surgery in terms of periapical healing, gain of periodontal support, PD reduction, and PRP may be an alternative treatment for GTR membrane in the treatment of apicomarginal defects.

In vitro evaluation of antioxidants of fruit extract of Momordica charantia L. on fibroblasts and keratinocytes.

The antioxidant activity of the total aqueous extract (TAE) and total phenolic extract (TPE) of Momordica charantia fruits was assayed by radical-scavenging methods and cytoprotective effects on hydrogen peroxide (H(2)O(2))- and hypoxanthin-xanthin oxidase (HX-XO)-induced damage to rat cardiac fibroblasts (RCFs), NIH 3T3, and keratinocyte (A431). Cell viability was monitored by a 3-[4,5-dimethyltriazol-2-yl]-2,5-diphenyltretrazolium (MTT) assay. For fibroblasts, TPE at 200 and 300 microg/mL showed maximum and consistent cytoprotection against oxidants. The extract at 50 microg/mL also had significant and slightly protective effects on fibroblasts against H(2)O(2)- and HX-XO-induced damage, respectively. RCF was more tolerant toward the damage. For keratinocytes, a dose-dependent relationship of oxidant toxicity was only seen with H(2)O(2) but the protective action of the extract correlated with oxidant dosage. At 200 and 300 microg/mL TPE, cytoprotection was dose-dependent against oxidants. Extracts had no effect on HX-XO toxicity at 50 microg/mL. Pretreatment with both the extracts did not show any cytoprotection.

Preparation and clinical evaluation of succinylated collagen punctal plugs in dry eye syndrome: a pilot study.

AIM: This is a pilot study of 10 eyes of 6 patients. This paper describes the preparation and clinical evaluation of succinylated collagen punctal plugs (SCPP) in the treatment of dry eye syndrome (DES). METHODS: SCPP were prepared from succinylated collagen with the exact dimensions of the punctum (length 1.5-2.5 mm, diameter 0.2-0.5 mm, water content between 50 and 55%). All the patients were clinically evaluated for best corrected visual acuity (BCVA), tear fluid levels (TFL), protein content, tear fluid osmolarity (TFO), fluorescence staining of the cornea and tear break-up time (TBUT) before and after punctal occlusion with SCPP. RESULTS: TFL improved among all the patients after punctal occlusion with SCPP. BCVA showed improvement in case 4 (right eye/left eye), case 5 (left eye) and case 6 (right eye), who had developed dry eyes due to environmental conditions. Protein content increased on day 7 in all the patients and gradually decreased. TFO decreased on days 3 and 5 in all patients after punctal occlusion with SCPP, and showed the same levels on day 14. TFL, PC, TFO and TBUT showed significant improvement in all the patients after punctal occlusion with SCPP. CONCLUSION: All patients experienced symptomatic relief after punctal occlusion with SCPP. There was no discomfort, foreign body sensation, plug extrusion, corneal aberration, infection, or formation of pyogenic granuloma with SCPP. SCPP stands as a promising alternative to other punctal plugs in the treatment of DES.

Optimization of influential parameters for extracellular keratinase production by Bacillus subtilis (MTCC9102) in solid state fermentation using Horn meal--a biowaste management.

A Bacillus subtilis (MTCC9102) isolate was shown to produce significant amount of keratinase under optimized conditions in solid-state fermentation using Horn meal as a substrate. Optimized value for moisture, inoculum, and aeration were found to be 100% (v/w), 50% (v/w), and 150% (w/w), respectively, and the optimum nitrogen source was peptone and carbon source was dextrose. Maximum keratinolytic activity was observed at 48 h after incubation, and the optimum age (24 h) of inoculum was significant. The influence of cultivation temperature and initial pH of the medium on keratinase production revealed the optimum values for the temperature and pH as 37 degrees C and 7, respectively. Maximum keratinase activity of the crude extract was 15,972 U/mg/ml. These results indicate that this bacterial strain shows a high biotechnological potential for keratinase production in solid-state fermentation, and use of the horn meal as the substrate can be implemented for keratinous solid wastes management.

Evaluation of antimicrobial efficacy of herbal alternatives (Triphala and green tea polyphenols), MTAD, and 5% sodium hypochlorite against Enterococcus faecalis biofilm formed on tooth substrate: an in vitro study.

INTRODUCTION: The purpose of this study was to evaluate the antimicrobial efficacy of Triphala, green tea polyphenols (GTP), MTAD, and 5% sodium hypochlorite against E. faecalis biofilm formed on tooth substrate. METHODS: Extracted human teeth were biomechanically prepared, vertically sectioned, placed in the tissue culture wells exposing the root canal surface to E. faecalis to form a biofilm. At the end of the 3rd and 6th weeks all groups were treated for 10 minutes with the test solutions and control and were analyzed qualitatively and quantitatively. RESULTS: Qualitative assay with 3-week biofilm showed complete inhibition of bacterial growth with Triphala, MTAD and NaOCl, except GTP and saline, which showed presence of bacterial growth. In quantitative analysis, GTP- and saline-treated tooth samples have shown 1516 +/- 17.2 CFU/mL, 156.4 x 10(9) +/- 3.1 x 10(9) CFU/mL respectively. Qualitative assay with 6-week biofilm showed growth when treated with Triphala, GTP and MTAD whereas NaOCl has shown complete inhibition. All groups except NaOCl showed eight log reduction when compared to control when analyzed quantitatively. CONCLUSIONS: 5% sodium hypochlorite showed maximum antibacterial activity against E. Faecalis biofilm formed on tooth substrate. Triphala, green tea polyphenols and MTAD showed statistically significant antibacterial activity. The use of herbal alternatives as a root canal irrigant might prove to be advantageous considering the several undesirable characteristics of NaOCl.

Biocompatibility of choline salts as crosslinking agents for collagen based biomaterials.

A series of novel choline based salts, some of which can be described as ionic liquids, are prepared and evaluated for their biocompatibility; when combined with collagenous biomaterials they exhibit good cell viability and adhesion properties as required for biomedical implant applications.

Fruit extracts of Momordica charantia potentiate glucose uptake and up-regulate Glut-4, PPAR gamma and PI3K.

ETHNOPHARMACOLOGICAL RELEVANCE: Momordica charantia fruit is a widely used traditional medicinal herb as, anti-diabetic, anti-HIV, anti-ulcer, anti-inflammatory, anti-leukemic, anti-microbial, and anti-tumor. AIMS OF STUDY: The present study is undertaken to investigate the possible mode of action of fruit extracts derived from Momordica charantia (MC) and study its pharmacological effects for controlling diabetic mellitus. Effects of aqueous and chloroform extracts of Momordica charantia fruit on glucose uptake and up-regulation of glucose transporter (Glut-4), peroxisome proliferator activator receptor gamma (PPAR gamma) and phosphatidylinositol-3 kinase (PI3K), were investigated to show its efficacy as a hypoglycaemic agent. MATERIALS AND METHODS: Dose dependent glucose uptake assay was performed on L6 myotubes using 2-deoxy-D-[1-(3)H] glucose. Up-regulatory effects of the extracts on the mRNA expression level of Glut-4, PPAR gamma and PI3K have been studied. RESULTS: The association of Momordica charantia with the aqueous and chloroform extracts of Momordica charantia fruit at 6 microg/ml has shown significant up-regulatory effect, respectively, by 3.6-, 2.8- and 3.8-fold on the battery of targets Glut-4, PPAR gamma and PI3K involved in glucose transport. The up-regulation of glucose uptake was comparable with insulin and rosiglitazone which was approximately 2-fold over the control. Moreover, the inhibitory effect of the cyclohexamide on Momordica charantia fruit extract mediated glucose uptake suggested the requirement of new protein synthesis for the enhanced glucose uptake. CONCLUSION: This study demonstrated the significance of Glut-4, PPAR gamma and PI3K up-regulation by Momordica charantia in augmenting the glucose uptake and homeostasis.

Evaluation of succinylated collagen bandage lenses in corneal healing by the expression of matrix metalloproteinases (MMP-2 and MMP-9) in tear fluid.

AIM: The aim of the study was to evaluate the efficacy of succinylated collagen bandage lenses (SCBL) in the healing of various corneal conditions. METHODS: Clinical evaluation of SCBL was carried out in patients with corneal ulcer (CU), recurrent corneal erosions (RCE), dry eyes (DE) and corneal lesion (CL). In each patient, corneal healing was studied by subjective clinical assessment such as pain, redness, watering, discomfort, irritation, foreign body sensation, biochemical analysis of tear fluid (TF) for protein content, expression of matrix metalloproteinases (MMPs) by gelatin zymography (GZ) and Western blotting (WB). In both GZ and WB bands were quantified and analyzed by gel documentation analyzer. RESULTS: Subjective clinical assessment of CU, RCE, DE and CL patients after treatment with SCBL showed significant reduction in the symptoms, patients felt comfortable with SCBL with no change in visual acuity, indicating complete transparency of SCBL. Protein content was very high on day 1 among all the patients, and it reduced gradually after treatment with SCBL signifying corneal healing. GZ of TF showed the expression of both MMP-2 and MMP-9 on day 3. There was significant reduction in MMP-2 and MMP-9 expression on day 7 in all cases, it decreased considerably on day 14 and was almost negligible on day 21 reflecting corneal healing with SCBL. CONCLUSION: Our study indicated that SCBL significantly reduces symptoms of irritation and discomfort in the cornea. It maintains visual acuity, controls inflammation and watering in the eye reflecting corneal healing in all cases studied by us. SCBL represents a promising alternative to other bandage lenses in corneal healing.

Clinical evaluation of succinylated collagen bandage lenses for ophthalmic applications.

AIM: To study whether succinylated collagen bandage lenses (SCBL) prepared from modified bovine collagen (succinylated collagen) can replace other bandage lenses presently employed to treat various corneal conditions like filamentary keratitis, dry eyes, recurrent corneal erosions, foreign body removal and epithelial trauma. METHODS: This observational case study included 32 patients (22 female and 10 male): 8 patients for filamentary keratitis (25%), 10 patients for dry eyes (31%), 4 patients for recurrent corneal erosions (13%), 7 patients for foreign body removal (22%) and 3 patients for epithelial trauma (9%). Their eyes were evaluated for biocompatibility, in vivo transparency, patient comfort, corneal fit, best corrected visual acuity (BCVA), tear fluid level and dissolution rate of SCBL. This was carried out over a 24-hour period of time. RESULTS: SCBL exhibited good transparency and remained transparent throughout the period of study (between 0 and 24 h) in the eyes of patients. SCBL did not cause any irritation, discomfort and foreign body sensation in the eye and eyes remained comfortable throughout the experiment. BCVA in the control group of patients was 1.00 (20/20). Mean (+/-SD) BCVA before inserting SCBL (in decimal equivalent) was 0.31 (20/60) +/- 0.18 (range 0.1- 0.66). BCVA (+/-SD) changed to 0.25 (20/80) +/- 0.18 4 h after the application of SCBL and 0.27 (20/70) +/- 0.18 24 h after the application of SCBL, with a safety index of 1.20. The mean (+/-SD) tear fluid level before application of SCBL was 11.9 +/- 5.39 h (range 3-24 mm) and changed to 13.9 +/- 5.68 h (range 5-28 mm) after 4 h of application of SCBL and 15.9 +/- 5.72 h (range 7-30 mm) after 24 h with a safety index of 13 mm. The mean (+/-SD) dissolution rate of SCBL in the control group of patients was 17.8 +/- 8.65 h (range 10-24 h) and the mean (+/-SD) dissolution rate in the experimental group was 22.2 +/- 9.29 h (range 10-24 h). We report the use of SCBL in various corneal conditions. CONCLUSION: The present study showed that SCBL has complete corneal fit and good comfort in human eyes. Transparency was maintained for a longer period along with fair visual acuity and improvement in tear fluid levels. The disadvantages of other bandage lenses presently used to treat various corneal conditions could be overcome by the use of SCBL lenses.

A novel method to measure oxygen permeability and transmissibility of contact lenses.

PURPOSE: The present paper describes an accurate and cost-effective method requiring simple equipment to measure the oxygen permeability and transmissibility of contact lenses. METHOD: The method involves accurate measurement of oxygen across the material by allowing the gas (oxygen) to pass through the lens material in a specially fabricated lens mould. The expelled gas is collected by dissolution in ethanol and the oxygen is measured by titration of the solvent. RESULT: This method is suitable for the measurement of oxygen permeability and transmissibility of contact lenses of varying thickness and different radii of curvature. It can measure Dk and Dk/t of collagen bandage lenses in both wet and dry conditions. CONCLUSION: The oxygen permeability and transmissibility values obtained by this method were compared with the oxygen permeability standard values of commercially available contact lenses and the results are summarised.

Evaluation of the inhibitory effect of triphala on PMN-type matrix metalloproteinase (MMP-9).

BACKGROUND: This study evaluated the inhibitory activity of triphala on PMN-type matrix metalloproteinase (MMP-9) expressed in adult periodontitis patients and compared its activity with another ayurvedic drug, kamillosan, and doxycycline, which has known inhibitory activity. METHODS: Matrix metalloproteinases (MMPs) were extracted from gingival tissue samples from 10 patients (six males, four females) with chronic periodontitis. Tissue extracts were treated with the drug solutions, the inhibition was analyzed by gelatin zymography, and the percentage of inhibition was determined by a gel documentation system. RESULTS: The activity of MMPs was significantly decreased with the use of the drugs. Triphala showed a 76.6% reduction of MMP-9 activity, whereas kamillosan showed a 46.36% reduction at a concentration of 1,500 microg/ml (crude extract) and doxycycline showed a 58.7% reduction at a concentration of 300 microg/ml (pure drug). CONCLUSION: The present study showed the strong inhibitory activity of triphala on PMN-type MMPs involved in the extracellular matrix (ECM) degradation during periodontitis.

Alpha-crystallin-incorporated collagen matrices as an aid for dermal wound healing.

This study evaluated the effects of noncovalently incorporated crystallin into the collagen matrix for dermal wound-healing processes in rats. Crystallin-incorporated collagen matrix (CIC) showed better healing when compared to wounds treated with collagen matrix (CS) and without collagen (CR). Biochemical parameters and histological analysis revealed that increased wound contraction enhanced cell proliferation and efficient radical scavenging in the CIC group. The higher shrinkage temperature of CIC films when compared to CS groups suggested increased hydrothermal stability for the former material. An in vitro release study of CIC has showed sustained and time-dependent release of crystallin from the collagen matrix. These results demonstrate the possibility of using crystallin as therapeutic protein in the wound-healing process.

Dermal wound healing processes with curcumin incorporated collagen films.

The wound healing process involves extensive oxidative stress to the system, which generally inhibits tissue remodeling. In the present study, an improvement in the quality of wound healing was attempted by slow delivery of antioxidants like curcumin from collagen, which also acts as a supportive matrix for the regenerative tissue. Curcumin incorporated collagen matrix (CICM) treated groups were compared with control and collagen treated rats. Biochemical parameters and histological analysis revealed that increased wound reduction, enhanced cell proliferation and efficient free radical scavenging in CICM group. The higher shrinkage temperature of CICM films suggests increased hydrothermal stability when compared to normal collagen films. Spectroscopic studies revealed that curcumin was bound to the collagen without affecting its triple helicity. Further we adopted the antioxidant assay using 2,2'-azobisisobutyronitrile to assess in vitro antioxidant activity of CICM. The antioxidant studies indicated that CICM quenches free radicals more efficiently. This study provides a rationale for the topical application of CICM as a feasible and productive approach to support dermal wound healing.

Development of a novel non-human primate model for preclinical gene vector safety studies. Determining the effects of intracerebral HSV-1 inoculation in the common marmoset: a comparative study.

The owl monkey (Aotus trivirgatus) has served as the standard non-human primate model of herpes simplex virus-1 (HSV-1) infection because it is highly susceptible to HSV-1 encephalitis. Owl monkeys, however, are expensive, difficult to obtain, and difficult to maintain in captivity, thus greatly hampering the efficiency of preclinical gene therapy trials for brain tumors using HSV-1-based vectors. We have therefore compared the susceptibility of the common marmoset (Callithrix jacchus) with the owl monkey in a model of intracerebral inoculation of wildtype HSV-1 F-strain at increasing titers. The common marmosets consistently succumbed earlier to viral encephalitis than the owl monkeys. The histological evaluation of the common marmoset revealed extensive HSV-1 infection with a concomitant yet less marked inflammatory response compared to the owl monkeys. PCR for HSV-1 demonstrated a similar extra-CNS shedding route in both experimental models. Our findings show that the common marmoset is at least as susceptible to intracerebral HSV-infection as the owl monkey and that it can therefore serve as a valid and reliable experimental model for the important preclinical safety tests of HSV-based therapeutic viral vector constructs in the brain.

Prolonged dominance of clonally restricted CD4(+) T cells in macaques infected with simian immunodeficiency viruses.

The repertoire of functional CD4(+) T lymphocytes in human immunodeficiency virus type 1-infected individuals remains poorly understood. To explore this issue, we have examined the clonality of CD4(+) T cells in simian immunodeficiency virus (SIV)-infected macaques by assessing T-cell receptor complementarity-determining region 3 (CDR3) profiles and sequences. A dominance of CD4(+) T cells expressing particular CDR3 sequences was identified within certain Vbeta-expressing peripheral blood lymphocyte subpopulations in the infected monkeys. Studies were then done to explore whether these dominant CD4(+) T cells represented expanded antigen-specific cell subpopulations or residual cells remaining in the course of virus-induced CD4(+) T-cell depletion. Sequence analysis revealed that these selected CDR3-bearing CD4(+) T-cell clones emerged soon after infection and dominated the CD4(+) T-cell repertoire for up to 14 months. Moreover, inoculation of chronically infected macaques with autologous SIV-infected cell lines to transiently increase plasma viral loads in the monkeys resulted in the dominance of these selected CDR3-bearing CD4(+) T cells. Both the temporal association of the detection of these clonal cell populations with infection and the dominance of these cell populations following superinfection with SIV suggest that these cells may be SIV specific. Finally, the inoculation of staphylococcal enterotoxin B superantigen into SIV-infected macaques uncovered a polyclonal background underlying the few dominant CDR3-bearing CD4(+) T cells, demonstrating that expandable polyclonal CD4(+) T-cell subpopulations persist in these animals. These results support the notions that a chronic AIDS virus infection can induce clonal expansion, in addition to depletion of CD4(+) T cells, and that some of these clones may be SIV specific.

Identifying the target cell in primary simian immunodeficiency virus (SIV) infection: highly activated memory CD4(+) T cells are rapidly eliminated in early SIV infection in vivo.

It has recently been shown that rapid and profound CD4(+) T-cell depletion occurs almost exclusively within the intestinal tract of simian immunodeficiency virus (SIV)-infected macaques within days of infection. Here we demonstrate (by three- and four-color flow cytometry) that this depletion is specific to a definable subset of CD4(+) T cells, namely, those having both a highly and/or acutely activated (CD69(+) CD38(+) HLA-DR(+)) and memory (CD45RA(-) Leu8(-)) phenotype. Moreover, we demonstrate that this subset of helper T cells is found primarily within the intestinal lamina propria. Viral tropism for this particular cell type (which has been previously suggested by various studies in vitro) could explain why profound CD4(+) T-cell depletion occurs in the intestine and not in peripheral lymphoid tissues in early SIV infection. Furthermore, we demonstrate that an acute loss of this specific subset of activated memory CD4(+) T cells may also be detected in peripheral blood and lymph nodes in early SIV infection. However, since this particular cell type is present in such small numbers in circulation, its loss does not significantly affect total CD4(+) T cell counts. This finding suggests that SIV and, presumably, human immunodeficiency virus specifically infect, replicate in, and eliminate definable subsets of CD4(+) T cells in vivo.

The disruption of macaque CD4+ T-cell repertoires during the early simian immunodeficiency virus infection.

T-cell receptor (TCR) complementarily determining region 3 (CDR3) spetratyping analysis was employed to assess the ability of an AIDS virus to disrupt CD4 + T-cell repertoires during the primary infection. Rhesus and pig-tailed macaques infected with simian immunodeficiency virus (SIV)mac 251 and SIVsmmFGb, respectively, were evaluated. Following SIV infection, the macaques exhibited an apparent decline of CD4 + peripheral blood lymphocyte (PBL) counts, which was associated with a change in CDR3 profiles from multiple-length distribution to one- or two-length dominance in the selected TCR Vbeta-expressing CD4 + PBL subpopulations. Molecular analysis of the perturbed cell subpopulations suggested that the CD4 + T cells bearing the dominant CDR3 length were clonally expanded. These results indicate that SIV infection can induce a disruption of macaque CD4 + T-cell repertoires during the primary infection. The finding in this study, therefore, suggests that the virus-induced clonal dominance can contribute to the disruption of CD4 + T-cell repertoires.