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Biomedical subjects

N Bhatia

Publications and source records attributed to N Bhatia.

At least 19 recordsLinked to original sources

Green tea polyphenol EGCG suppresses cigarette smoke condensate-induced NF-kappaB activation in normal human bronchial epithelial cells.

Cigarette smoke is a powerful inducer of inflammatory responses resulting in disruption of major cellular pathways with transcriptional and genomic alterations driving the cells towards carcinogenesis. Cell culture and animal model studies indicate that (-)-epigallocatechin-3-gallate (EGCG), the major polyphenol present in green tea, possesses potent anti-inflammatory and antiproliferative activity capable of selectively inhibiting cell growth and inducing apoptosis in cancer cells without adversely affecting normal cells. Here, we demonstrate that EGCG pretreatment (20-80 microM) of normal human bronchial epithelial cells (NHBE) resulted in significant inhibition of cigarette smoke condensate (CSC)-induced cell proliferation. Nuclear factor-kappaB (NF-kappaB) controls the transcription of genes involved in immune and inflammatory responses. In most cells, NF-kappaB prevents apoptosis by mediating cell survival signals. Pretreatment of NHBE cells with EGCG suppressed CSC-induced phosphorylation of IkappaBalpha, and activation and nuclear translocation of NF-kappaB/p65. NHBE cells transfected with a luciferase reporter plasmid containing an NF-kappaB-inducible promoter sequence showed an increased reporter activity after CSC exposure that was specifically inhibited by EGCG pretreatment. Immunoblot analysis showed that pretreatment of NHBE cells with EGCG resulted in a significant downregulation of NF-kappaB-regulated proteins cyclin D1, MMP-9, IL-8 and iNOS. EGCG pretreatment further inhibited CSC-induced phosphorylation of ERK1/2, JNK and p38 MAPKs and resulted in a decreased expression of PI3K, AKT and mTOR signaling molecules. Taken together, our data indicate that EGCG can suppress NF-kappaB activation as well as other pro-survival pathways such as PI3K/AKT/mTOR and MAPKs in NHBE cells, which may contribute to its ability to suppress inflammation, proliferation and angiogenesis induced by cigarette smoke.

Anticarcinogenic Agents↗

Effect of rehabilitation facility location on outcomes in head and neck surgical patients.

The objective of this study was to determine the significance of in-hospital rehabilitation facility vs. distant rehabilitation facilities in the outcomes and complications of post-operative head and neck surgical patients. Retrospective review of head and neck surgical patients was conducted over a 5-year period at a tertiary care medical centre. Fifty patients met criteria for this study (35 males, 15 females). Forty-two patients had a primary squamous cell carcinoma and eight patients had other primary malignancies of the head and neck. Thirty-two patients were placed in an in-hospital rehabilitation facility and 18 patients were placed in distant rehabilitation facilities (average distance 40.9 miles). Seventeen patients (34%) had complications including infection/drainage (seven patients), fistula (six patients), pneumonia (two patients), wound dehiscence (two patients) and other minor complications. The difference complication rate among the two groups was not statistically significant (37.5% in-hospital rehabilitation, 27.8% distant rehabilitation; P=0.496). The rate of hospital re-admission was not statistically significant (25% in-hospital rehabilitation patients, 16.7% distant rehabilitation patients; P=0.505). The average length of stay of patients without complications was 18.5 days (SD=5.8) for in-hospital rehabilitation and 12.9 days (SD=17) for distant rehabilitation. This difference was not statistically significant (P=0.346). In summary, one-third of post-operative head and neck surgical patients developed complications while in a rehabilitation facility. The length of stay, hospital re-admission rate and frequency of complications does not correlate with the proximity of the rehabilitation facility to the hospital where the patients received their surgery.

Aged↗

Arthroscopic reconstruction of the anterior cruciate ligament using bone-patellar tendon-bone autograft: experience of the first 100 cases.

PURPOSE: To review the results of patients who underwent arthroscopic reconstruction of the anterior cruciate ligament (ACL) via a single incision technique using a bone-patellar tendon-bone autograft. METHODS: Patients with ACL-deficient knees who were symptomatic and wanted to maintain an active lifestyle or continue sporting activities were included. ACL reconstruction using the bone-patellar tendon-bone graft was performed on 100 patients. One-year follow-up was completed in 78 patients who were then reviewed. The mean age of patients reviewed was 26.8 years (range, 21-39 years), of whom 35 (44.9%) were aged between 26 and 30 years. There were 73 men and 5 women (ratio, 14.6:1). Injuries on the right side outnumbered those on the left (44 versus 34). Sports injuries accounted for 66.7% (n = 52) of patients, motor vehicle accidents and household injuries accounted for 30.8% (n = 24) and 2.6% (n = 2), respectively. RESULTS: Excellent and good-to-excellent results were achieved in 7 (9%) and 61 (78.2%) of patients. Residual anterior knee pain (n = 18) was the most common complication, followed by difficulty in regaining full range of motion (n = 10) and divergence of femoral screw (n = 9). CONCLUSION: This procedure provides consistent and reproducible results in carefully selected patients and allows them an early return to sporting activities with minimal residual morbidity.

Adult↗

Multicenter clinical trials on a novel polyherbal formulation in allergic rhinitis.

Allergic rhinitis is the most frequently occurring immunological disorder. It affects men, women and children and represents significant cost in terms of suffering and loss of productivity. Allergy is termed as an excessive reaction to an environmental allergen. Pollen, mold, dust, mite and animal allergens that contact the nasal or eye lining cause sneezing, nasal congestion and itchy, watery, swollen, red eyes. Although a broad spectrum of therapeutic options is available, the treatment of allergic rhinitis appears to be far from satisfactory. A novel polyherbal formulation (PF; Aller-7/NR-A2) comprising seven medicinal herbal extracts was assessed in a multicenter clinical trial involving 545 patients (321 males and 224 females) aged 18-59 years for 12 weeks to evaluate its clinical efficacy in patients suffering from allergic rhinitis. A total of 171 patients participated in double-blind, randomized, placebo-controlled studies in three centers, while 374 patients were included in the open-label studies in 11 centers. The three major symptoms (sneezing, rhinorrhea and nasal congestion) of allergic rhinitis were significantly reduced. Significant improvement was also observed in absolute eosinophil count, mucociliary clearance time, peak expiratory flow rate and peak nasal flow rate. No serious adverse events that warranted cessation of treatment were observed. Minor adverse effects were noted in both the treatment and placebo groups. Thus, this study demonstrates that Aller-7/NR-A2 is well tolerated and efficacious in patients with allergic rhinitis.

Adult↗

Tooth wear prevention: a quantitative and qualitative in vitro study.

BACKGROUND: Management of tooth wear from grinding presents a significant clinical challenge. Acrylic nightguards are often used to protect the teeth, but many patients still grind with these appliances. This study aimed to test the effectiveness of three lubricants in reducing enamel wear by using an electro-mechanical machine under controlled conditions, with a view to undertaking a subsequent longitudinal clinical study. METHODS: Sectioned tooth specimens were worn against each other under different loads and with the addition of three different lubricants: calcium fluoride (CaF) powder, olive-oil, and a combination of calcium fluoride with olive-oil in the form of a slurry. Wear rates of enamel only were quantified by weighing the specimens, and resin replicas of the worn tooth surfaces were made for examination under a scanning electron microscope. RESULTS: All three lubricants reduced the amount of enamel wear significantly compared with wearing specimens without adding lubricants. Wear rate was influenced by the type of lubricant and the load applied. Wear rates were significantly less for olive-oil and the olive-oil/CaF slurry compared with CaF alone. The microwear detail differed between the three lubricants. CONCLUSIONS: This study has shown that enamel wear can be reduced using dry or wet lubricants between opposing teeth that are worn under controlled conditions. Further research is required to clarify their possible clinical applications.

Analysis of Variance↗

Oxidant, vitamin A and angiogenic markers in laryngeal cancer patients.

In this study the status of oxidant stress, vitamin A and angiotensin-converting enzyme (ACE) levels were evaluated in cases of laryngeal carcinoma patients from Northern India. In control subjects the levels of malondialdehyde (MDA), vitamin A and ACE were 0.23 +/- 0.07 nmole/ml, 2515 +/- 84 IU, and 1.4 +/- 0.8 U/ml respectively. Thirty laryngeal cancer patients were divided into three groups according to the TNM classification (American Joint Committee on Cancers). In laryngeal cancer patients according to tumour size, MDA and ACE levels increased to 0.32 +/- 0.04 nmole/ml and 4.7 +/- 0.5 U/ml respectively and the effect was statistically significant (p<0.01). The correlation coefficient between different subgroups was also highly significant (r=0.96, p<0.01). However, serum vitamin A levels decreased to 621 +/- 20 IU and the effect was statistically significant (p<0.01). In another two groups of laryngeal cancer patients, a similar pattern of various markers was obtained. Thirty patients with laryngeal carcinoma were divided into four different groups according to nodal involvement and it was observed that in laryngeal cancer patients with no nodal involvement, ACE levels were low 3.6 +/- 1.4 U/ml while patients with maximum nodal involvement had the highest levels of ACE 7.1 +/- 0.18 U/ml. The correlation coefficient between different groups is highly statistically significant (r=0.95, p<0.01). In patients with laryngeal cancer the serum MDA and vitamin A levels correlation coefficient between different groups was not significant. It is thus concluded that serum ACE might be a specific test marker for laryngeal cancer disease burden. The use of this marker enzyme for therapeutics is being planned.

Female↗

Interparticle migration of metal cations in stream sediments as a factor in toxics transport.

Sorption of metal cations by stream sediments is an important process affecting the movement of released contaminants in the environment. The ability of cations to desorb from one sediment particle and subsequently sorb to another can greatly affect metal transport rates but rates for this process have not been reported. The objective of this study was to determine the rate at which sorbed metals can migrate from contaminated sediment particles to uncontaminated sediment particles as a function of the concentration of the contaminating solution and the duration of the contact with the contaminating solution. Samples of small sediment particles were exposed to solutions containing cobalt, after which they were rinsed and combined with larger uncontaminated sediment particles in the presence of stream water. Initial concentrations of the contaminating solution ranged from 1ng/l to 1000mg/l and exposures to the contaminating solution ranged from 6h to 14 days. The rate of the migration increased with increasing concentrations in the contaminating solution and with decreasing times of exposure to the contaminating solution. Under the conditions of these experiments, the time required for the migration to reach equilibrium was on the order of months or longer. In separate experiments, the kinetics of adsorption and desorption of cobalt were measured as a function of concentration of the contaminating solution. The time required to reach adsorption equilibrium increased with increasing concentration in the contaminating solution. Times to sorption equilibrium were on the order of months. Desorption was much slower than adsorption and, together with intraparticle diffusion, probably controls the rate of migration from contaminated to uncontaminated sediment. The results of this study show that interparticle migration of metal cations can proceed at significant rates that are strongly influenced by the length of time that the metal has been in contact with the sediment.

Adsorption↗

Detrimental effect of cancer preventive phytochemicals silymarin, genistein and epigallocatechin 3-gallate on epigenetic events in human prostate carcinoma DU145 cells.

BACKGROUND: Targeting epigenetic events associated with autonomous growth of advanced prostate cancer (PCA) is a practical approach for its control, prevention, and treatment. Recently we showed that treatment of prostate carcinoma DU145 cells with cancer preventive flavonoid silymarin at 100-200 microM doses inhibits erbB1-Shc mitogenic signaling and modulates cell cycle regulators leading to a G1 arrest and inhibition of cell growth and anchorage-independent colony formation. Here, we asked the question whether these important findings could be extended to other cancer preventive flavonoids and isoflavones such as epigallocatechin 3-gallate (EGCG) and genistein. METHODS: DU145 cells were treated with similar doses (100-200 microM) of silymarin, genistein or EGCG, cell lysates prepared, and levels of activated signaling molecules (erbB1-Shc-ERK1/2) and cell cycle regulators (CDKIs, CDKs, and cyclins) analyzed employing immunoprecipitation and/or immunoblotting techniques. Cell growth studies were done by cell counting during 5 days of treatment with these agents, and cell death was determined by Trypan blue staining. RESULTS: Treatment of cells with silymarin, genistein or EGCG at 100-200 microM resulted in a complete inhibition of TGFalpha-caused activation of erbB1 followed by a moderate to strong inhibition (10-90%) of Shc activation without an alteration in their protein levels. Silymarin and genistein, but not EGCG, also inhibited (10% to complete) ERK1/2 activation suggesting that these agents impair erbB1-Shc-ERK1/2 signaling in DU145 cells. In other studies, silymarin, genistein or EGCG caused a strong induction of Cip1/p21 (up to 2.4-fold) and Kip1/p27 (up to 150-fold), and a strong decrease in CDK4 (40-90%) but had moderate effect on CDK2, and cyclins D1 and E. An enhanced level of CDKIs also led to an increase in their binding to CDK4 and CDK2. Treatment of cells with silymarin, genistein or EGCG also resulted in 50-80% cell growth inhibition at lower doses, and complete inhibition at higher doses. In contrast to silymarin, higher doses of genistein showed cytotoxic effect causing 30-40% cell death. A more profound cytotoxic effect was observed with EGCG accounting for 50% cell death at lower doses and complete loss of viability at higher doses. CONCLUSIONS: These results suggest that similar to silymarin, genistein and EGCG also inhibit mitogenic signaling pathway(s) and alter cell cycle regulators, albeit at different levels, leading to growth inhibition and death of advanced and androgen-independent prostate carcinoma cells. More studies are, therefore, needed with these agents to explore their anti-carcinogenic potential against human prostate cancer.

Adaptor Proteins, Signal Transducing↗

Compartmentalized bone regeneration of cranial defects with biodegradable barriers: an animal model.

In bony defects of the cranium, bone healing may be complicated by prolapse of surrounding tissue into the defect. This tissue acts as an impediment to prevent the migration of osteogenic cells, leading to impaired bone formation. It has been previously shown that a membrane placed over the bony defect inhibits the connective tissue cells from entering the wound and theoretically improves bone formation. The use of a proven resorbable material, Lactosorb, is used in this animal model and has shown a significant increase in autogenous bony formation. The majority of previous work was accomplished with nonresorbable material that resulted in foreign body formation. This paper is unique because resorbable material in the animal model is relatively inexpensive and easy to use and has allowed successful autogenous bony regeneration.

Absorbable Implants↗

Differential responses of skin cancer-chemopreventive agents silibinin, quercetin, and epigallocatechin 3-gallate on mitogenic signaling and cell cycle regulators in human epidermoid carcinoma A431 cells.

Silibinin, quercetin, and epigallocatechin 3-gallate (EGCG) have been shown to be skin cancer-preventive agents, albeit by several different mechanisms. Here, we assessed whether these agents show their cancer-preventive potential by a differential effect on mitogenic signaling molecules and cell cycle regulators. Treatment of human epidermoid carcinoma A431 cells with these agents inhibited the activation of the epidermal growth factor receptor and the downstream adapter protein Shc, but only silibinin showed a marked inhibition of mitogen-activated protein kinase-extracellular signal-regulated kinase-1 and -2 activation. In terms of cell cycle regulators, silibinin treatment showed an induction of Cip1/p21 and Kip1/p27 together with a significant decrease in cyclin-dependent kinase (CDK)-4, CDK2, and cyclin D1. Quercetin treatment, however, resulted in a moderate increase in Cip1/p21 with no change in Kip1/p27 and a decrease in CDK4 and cyclin D1. EGCG treatment also led to an induction of Cip1/p21 but no change in Kip1/27, CDK2, and cyclin D1 and a decrease in CDK4 only at low doses. Treatment of cells with these agents resulted in a strong dose- and time-dependent cell growth inhibition. A high dose of silibinin and low and high doses of quercetin and EGCG also led to cell death by apoptosis, suggesting that a lack of their inhibitory effect on mitogen-activated protein kinase-extracellular signal-regulated kinase-1 and -2 activation possibly "turns on" an apoptotic cell death response associated with their cancer-preventive and anticarcinogenic effects. Together, these results suggest that silibinin, quercetin, and EGCG exert their cancer-preventive effects by differential responses on mitogenic signaling and cell cycle regulators.

Adaptor Proteins, Signal Transducing↗

Identification of amastigote-specific antigens of Leishmania donovani using kala-azar patient sera.

Antigenic characterization of the soluble fraction of axenic amastigotes of Leishmania donovani ( strain Dd8, causative agent of Indian kala-azar) and their comparison with promastigotes is reported. The axenic amastigotes were assessed for their immunological status employing anti-A2 monoclonal antibody which is extremely specific for L. donovani amastigotes. SDS-PAGE of 35[S] methionine labeled proteins of the two parasite stages exhibited few stage specific and some conserved antigens in both the stages. An increased synthesis of heat shock proteins was observed in axenic amastigotes. Western blot experiments employing sera of kala azar positive patients identified immunodominent antigens of 116,83,26 and 12 kDa in axenic amastigotes which were not present in promastigotes. These amastigote stage specific antigens may have immense potential in immunodiagnosis and prophylaxis of kala-azar.

Animals↗

Aural foreign bodies.

At KGMC Lucknow, 168 pediatric cases with aural foreign bodies (FB) were reviewed. Most of the FB were self-inflicted and seen in children under 5 years of age (69.64%), within 24 hours (91.66%) of impaction. 86.30% of FB were seen to impact in external auditory canal (EAC) and their nature revealed predominance of nonvegetative inanimate FBs (43.45%). The TM perforation was encountered in only 6.54% of cases. If the FB is a living insect, it should be drowned before being manipulated. Syringing is the method of choice for a nonimpacted relatively small FB, even if it is vegetative. It is to be avoided in the 'potential' cases of external otitis or in cases with severely impacted wax. For a tightly wedged smooth rounded FB the hook and forceps are preferred in superficially and deep lying FBs respectively. A dissociate anaesthesia (ketamine) appears to be a better choice than general anaesthesia. An end-aural incision should be preferred over post-aural one and canalplasty for access of FB should be carried out wherever necessary. The presence of otorrhoea in cases of penetrating FB or aural myasis should be dealt on the lines of otitis media after removing the FB concerned.

Adolescent↗

Aerodigestive foreign bodies.

Accidents with foreign bodies (FBs) are most common within the first two years of life. The airway FBs present a diagnostic dilemma as both the history and the investigations can be misleading. The persistent hypoxia presents a threat to life as does extraction. Moreover, the chemical pneumonitis induced by vegetative FB makes the situation even more worse. The FB of digestive tract are comparatively benign unless long standing. It is neither necessary for the airway FB to present with respiratory symptoms and signs nor for the FB of digestive tract to complain of dysphagia/throat pain. Oesophagoscopy may have to be done if an esophageal FB is causing only recurrent respiratory infections without dysphagia. The situation in dealing with FB varies from site to site in the aerodigestive tract. This article stresses the various dubious factors including the history, examination and investigation which can lead to misdiagnosis and also those problems which are encountered during planned extraction as well as post-operatively.

Airway Obstruction↗

Inhibition of human carcinoma cell growth and DNA synthesis by silibinin, an active constituent of milk thistle: comparison with silymarin.

Several studies from our laboratory have shown the cancer chemopreventive and anti-carcinogenic effects of silymarin, a flavonoid antioxidant isolated from milk thistle, in long-term tumorigenesis models and in human prostate, breast and cervical carcinoma cells. Since silymarin is composed mainly of silibinin with small amounts of other stereoisomers of silibinin, in the present communication, studies were performed to assess whether the cancer preventive and anti-carcinogenic effects of silymarin are due to its major component silibinin. Treatment of different prostate, breast, and cervical human carcinoma cells with silibinin resulted in a highly significant inhibition of both cell growth and DNA synthesis in a time-dependent manner with large loss of cell viability only in case of cervical carcinoma cells. When compared with silymarin, these effects of silibinin were consistent and comparable in terms of cell growth and DNA synthesis inhibition, and loss of cell viability. Based on the comparable results of silibinin and silymarin, we suggest that the cancer chemopreventive and anti-carcinogenic effects of silymarin reported earlier are due to the main constituent silibinin.

Antineoplastic Agents, Phytogenic↗

Pregnancy following incontinence surgery.

A two-page questionnaire was distributed to 304 members of the American Urogynecology Society. Ninety-nine of the 149 respondents reported that they had performed continence surgery on patients who specifically stated their desire for future childbearing. One hundred and eleven recommended the Burch colposuspension, 29 favored the sling procedure, and others advocated different procedures. Urologists as a subset more often recommended either a sling or needle suspension. Twenty-eight percent of respondents felt a trial of labor and vaginal delivery was indicated following incontinence surgery, but 40% stated that they would always perform cesarean section in these patients. A total of 40 vaginal deliveries and 47 cesarean sections were reported. When postpartum continence status was known, only 73% of women who had vaginal deliveries were continent, whereas 95% were continent following cesarean section. Fisher's exact test revealed this to be a statistically significant difference (P = 0.0344).

Cesarean Section↗

Congenital syndromes associated with nonmelanoma skin cancer.

Syndromes associated with nonmelanoma skin cancer are part of a group of inherited disorders characterized by a wide variety of clinical manifestations including palmar and plantar pitting, calcification of the dura, jaw cysts, and skeletal abnormalities. The syndromes have in common skin lesions progressing to basal or squamous cell cancers. In addition to skin tumors, bone and visceral tumors are common. Early diagnosis, genetic counseling, and treatment of skin lesions are appropriate tools for the management of patients with these syndromes. Surgical procedures generally involve total resection combined with reconstructive efforts.

Basal Cell Carcinoma↗

'NESTROFT'--an effective screening test for beta thalassemia trait.

OBJECTIVE: To evaluate the efficacy of NESTROFT (Naked Eye Single Tube Red Cell Osmotic Fragility Test) as a screening tool for detection of beta thalassemia trait. DESIGN: Prospective study. SETTING: Field camps in various parts of Gujarat and Maharashtra States. METHODS: A total of 2525 subjects were screened. NESTROFT, complete hemogram including red cell indices and calculation of Mentzer's Fraction (MF) and discriminant functions (DF1-4) were done in all subjects. HbA2 was performed in 830 initial subjects to compute sensitivity, specificity and predictive values for various parameters. RESULTS: NESTROFT (sensitivity 94.4%), as a single screening parameter was superior to any of the other evaluated parameters individually, besides being cost effective. Mean corpuscular volume (MCV) < 80 fl followed NESTROFT closely (sensitivity 93.7; p > 0.05). MCV < 75 fl had a significantly (p < 0.001) lower sensitivity (87.3%) in comparison to both of these parameters. In contrast, MF, DF1, DF2, DF3 and DF4 did not meet the requirements of a good screening test with sensitivity values of 66.2%, 54.9%, 47.2%, 64.1% and 55.6%, respectively. NESTROFT in combination with MCV < 80 fl proved 100% sensitive. However, the combination was not cost effective. CONCLUSION: NESTROFT is a sensitive, cost effective, rapid and reliable screening test for detection of beta thalassemia trait in a population.

Adolescent↗