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Biomedical subjects

S K Pandey

Publications and source records attributed to S K Pandey.

At least 19 recordsLinked to original sources
PubMed2002

Post cataract-intraocular lens (IOL) surgery opacification.

Intraocular lens (IOL) implantation has no doubt been one of the most satisfying advances of medicine. Millions of individuals with visual disability or frank blindness from cataracts had and continue to have benefit from this procedure. It has been reported by ophthalmologists that the modern cataract-intraocular lens (IOL) surgery is safe and complication-free most of the time. This makes the watchword for any cataract surgeon to be 'implantation,' 'implantation,' 'implantation.' In the mid-1980s, as IOLs were evolving rapidly, the watchword of the implant surgeon was 'fixation,' 'fixation,' 'fixation.' Most techniques, lenses and surgical adjuncts now allow us to achieve the basic requirement for successful IOL implantation, namely long-term stable IOL fixation in the capsular bag. However despite this advancement some items 'slipped through cracks.' In this article, we would like to alert the reader to a new watchword, namely 'opacification,' 'opacification,' 'opacification.' Here we will be talking about the good, the bad, and the ugly. Examples of the 'good' include the recent successes now being achieved in reducing the incidence of posterior capsule opacification. Examples of the 'bad' include various proliferations of anterior capsule cells, problems caused by silicone oil adherence to IOLs and problems with piggyback IOLs. The 'ugly' include the sometimes striking and often visually disabling opacifications occurring on and within IOL optics, both on some modern foldable IOLs as well as a poly(methyl methacrylate) (PMMA) optic degradation occurring with some models a decade or more after implantation.

Cataract↗
PubMed2001

Constitutively active Akt is an important regulator of TRAIL sensitivity in prostate cancer.

TRAIL/Apo-2L is a member of the tumor necrosis factor superfamily and has recently been shown to induce apoptosis in cancer cells, but not in normal cells. In nude mice injected with human tumors, TRAIL reduces the size of these tumors without side effects. Akt promotes cell survival and block apoptosis. Some prostate cancer cells express high levels of Akt due to lack of active lipid phosphatase PTEN, a negative regulator of PI-3 kinase pathway, which may be responsible for drug resistance. The objective of this paper is to investigate the intracellular molecules that regulate TRAIL resistance. We have examined caspase-8 activity, BID cleavage, Akt activity, mitochondrial membrane potential (DeltaPsi(m)) and apoptosis in prostate cancer (LNCap, PC-3, PC-3M and DU145) cells treated with or without TRAIL. PC-3, PC-3M and DU145 cells are sensitive to TRAIL, whereas LNCap cells are resistant. LNCap cells express the highest level of constitutively active Akt, which is directly correlated with TRAIL resistance. TRAIL activates caspase-8 in all the cell lines. Downregulation of constitutively active Akt by PI-3 kinase inhibitors (wortmannin and LY-294002), dominant negative Akt or PTEN, renders LNCap cells sensitive to TRAIL. Inhibition of TRAIL sensitivity occurs at the level of BID cleavage. Inhibition of protein synthesis by cycloheximide also causes LNCap cells sensitive to TRAIL. Overexpression of Bcl-2 or Bcl-X(L) inhibits TRAIL-induced DeltaPsi(m) and apoptosis. Overexpression of constitutively active Akt in PC-3M cells (express very low levels of constitutively active Akt) restores TRAIL resistance. These data suggest that elevated Akt activity protects LNCap cells from TRAIL-induced apoptosis, and the PI-3 kinase/Akt pathway may inhibit apoptotic signals by inhibiting processing of BID. Thus, constitutively active Akt is an important regulator of TRAIL sensitivity in prostate cancer.

Androstadienes↗
PubMed2001

Pro-survival function of Akt/protein kinase B in prostate cancer cells. Relationship with TRAIL resistance.

Tumor necrosis factor superfamily member TRAIL/Apo-2L has recently been shown to induce apoptosis in transformed and cancer cells. Some prostate cancer cells express constitutively active Akt/protein kinase B due to a complete loss of lipid phosphatase PTEN gene, a negative regulator of phosphatidylinositol 3-kinase pathway. Constitutively active Akt promotes cellular survival and resistance to chemotherapy and radiation. We have recently noticed that some human prostate cancer cells are resistant to TRAIL. We therefore examined the intracellular mechanisms of cellular resistance to TRAIL. The cell lines expressing the highest level of constitutively active Akt were more resistant to undergo apoptosis by TRAIL than those expressing the lowest level. Down-regulation of constitutively active Akt by phosphatidylinositol 3-kinase inhibitors, wortmannin and LY294002, reversed cellular resistance to TRAIL. Treatment of resistant cells with cycloheximide (a protein synthesis inhibitor) rendered cells sensitive to TRAIL. Transfecting dominant negative Akt decreased Akt activity and increased TRAIL-induced apoptosis in cells with high Akt activity. Conversely, transfecting constitutively active Akt into cells with low Akt activity increased Akt activity and attenuated TRAIL-induced apoptosis. Inhibition of TRAIL sensitivity occurs at the level of BID cleavage, as caspase-8 activity was not affected. Enforced expression of anti-apoptotic protein Bcl-2 or Bcl-X(L) inhibited TRAIL-induced mitochondrial dysfunction and apoptosis. We therefore identify Akt as a constitutively active kinase that promotes survival of prostate cancer cells and demonstrate that modulation of Akt activity, by pharmacological or genetic approaches, alters the cellular responsiveness to TRAIL. Thus, TRAIL in combination with agents that down-regulate Akt activity can be used to treat prostate cancer.

Androstadienes↗
PubMed2001

[Complication profiles of posterior chamber intraocular lenses IOL). An analysis of 586 foldable and 2077 rigid explanted intraocular lenses].

BACKGROUND: Foldable intraocular lenses (IOL) have become increasingly preferred choice for IOL implantation after cataract removal. However, both foldable as well as rigid IOLs are not yet complication-free and may need explanation. MATERIAL AND METHODS: A total of 2663 explanted posterior chamber IOLs (PCIOLs) were accessioned at the Center for Research on Ocular Therapeutics and Biodevices between January 1988 and September 2000. The lenses were examined grossly using a Leitz/Wild M-8-Zoom stereomicroscope. The clinical reasons for explanation were documented for foldable as well as for rigid lenses. RESULTS: Of a total of 2663 explanted PCIOLs, 586 were foldable lenses and 2077 were rigid PMMA lenses The most frequent reason for explantation of all 2663 IOLs studied was decentration/dislocation. Optic and haptic damage and posterior capsule rupture were significantly more often a reason for explantation in several foldable designs compared to rigid PCIOLs. Whereas rigid designs lead more often to corneal decompensation. The percentage of explanted IOLs because of inflammatory reactions decreased significantly from 1994 to 2000. CONCLUSIONS: The complication profiles of rigid and foldable IOLs revealed some apparent differences due to the nature of the IOL biomaterials and designs. IOL optic/haptic damage was a common complication for foldable IOLs, whereas it was only discovered in single digits for rigid PMMA IOLs. The possible explanation for this is, that the soft and flexible biomaterials, from which all the foldable IOLs were manufactured, are easier to be damaged during folding, unfolding and insertion procedure. In our opinion this relative disadvantage of foldable IOLs is by far outweighed by the numerous advantages of the small incision cataract surgery. The decreasing inflammatory reactions can be explained by advances in surgical techniques, especially the secure in-the-bag fixation of IOLs.

Humans↗
PubMed2001

[Morphological autopsy findings in human eyes implanted with Ridley intraocular lenses].

BACKGROUND: Sir Harold Ridley's first cataract extraction with implantation of an intraocular lens (IOL) marked the beginning of a major change in the practice of ophthalmology. MATERIAL AND METHODS: Two human autopsy globes implanted with original Ridley IOLs were grossly examined from behind with the Miyake-Apple photographic technique. The anterior segments were evaluated histologically. One Ridley IOL was examined by scanning electron microscopy. RESULTS: Both IOLs maintained a clear visual axis and had been placed in the capsular sac. The right lens was decentered inferiorly, the left IOL was well centered. The posterior capsule showed only minimal capsular opacification. Scanning electron microscopy (SEM) of the explanted IOL showed a smooth, well polished surface. CONCLUSIONS: In this patient Ridley IOLs maintained an ideal visual rehabilitation of 20/20 in both eyes, 22 and 18 years postoperatively. One surprising finding was the presence of a square, truncated optic edge geometry, very similar to that seen in some modern foldable IOLs. In our opinion the absence of posterior capsule opacification of the Ridley IOL may have partially been a result of this nearly sharp optic edge, that we confirmed by SEM. Even 22 years after implantation the Ridley IOL showed a high finish quality. Many of Sir Harold Ridley's early concepts like the IOL placement in the posterior chamber and endocapsular implantation are now the standard of modern cataract surgery.

Aged↗
PubMed2001

Eradication of posterior capsule opacification: documentation of a marked decrease in Nd:YAG laser posterior capsulotomy rates noted in an analysis of 5416 pseudophakic human eyes obtained postmortem.

OBJECTIVE: (1) To report the neodymium:yttrium-aluminum-garnet (Nd:YAG) laser posterior capsulotomy rate (%) of eight rigid and foldable intraocular lens (IOL) designs in a series of 5416 pseudophakic human eyes obtained postmortem, accessioned in our center between January 1988 and January 2000. (2) To identify factors that are instrumental in reducing the incidence of posterior capsule opacification, (PCO, secondary cataract) and hence the need for Nd:YAG laser posterior capsulotomy. DESIGN: Comparative autopsy tissue analysis. PARTICIPANTS: A total of 5416 globes with posterior chamber intraocular lens (PC-IOLs) obtained postmortem received from Lions Eye Banks between 1988 and 2000. METHODS: Miyake-Apple posterior photographic technique. Special reference was given to the presence or absence of Nd:YAG laser posterior capsulotomy orifice on the posterior capsule of each eye. MAIN OUTCOME MEASURES: The Nd:YAG laser posterior capsulotomy rate (%) as of January 2000 was documented. In addition, the Nd:YAG laser posterior capsulotomy rate for each lens was plotted on a monthly basis for the same period, creating a computerized trend or "timeline" for each IOL style. RESULTS: Relatively high Nd:YAG laser posterior capsulotomy rates ranging from 20.3% to 33.4% were noted with four relatively older designs (high incidence of implantation between 1988 and the early 1990s). Four modern foldable IOLs manufactured from silicone and acrylic materials had significantly lower Nd:YAG laser posterior capsulotomy rates ranging from 0.9% (Alcon Acrysof) to 17.1%. The difference in Nd:YAG rates among the eight IOL designs was found to be significant (P < 0.0001, chi-square test). Comparing foldable versus rigid designs, the foldable IOLs were associated with a much lower Nd:YAG laser posterior capsulotomy rate (14.1% vs. 31.1%). CONCLUSIONS: By use of the six factors regarding surgical technique and IOL choice described in this article, we strongly believe that the overall incidence of PCO and hence the incidence of Nd:YAG laser posterior capsulotomy is now rapidly decreasing from rates as high as 50% in the 1980s to early 1990s. Surgical tools and IOLs are now available to bring these rates down to single digits. Careful application and use of these tools by surgeons can genuinely lead in the direction of virtual eradication of secondary cataract, the second most common cause of visual loss worldwide.

Cataract↗
PubMed2001

Anterior capsule opacification: correlation of pathologic findings with clinical sequelae.

OBJECTIVE: To evaluate the degree of anterior capsule opacification (ACO) in human eyes obtained postmortem containing various rigid and foldable posterior chamber intraocular lens (PC-IOL) designs and compare the findings with clinical sequelae of capsular shrinkage. DESIGN: Comparative autopsy tissue study with clinicopathologic correlations. MATERIALS: Three hundred formalin-fixed human eyes containing the following PC-IOL styles were analyzed: (1) one-piece polymethyl methacrylate (PMMA) optic-PMMA haptic (n = 50), one-piece silicone-plate IOL, with large (2) or small (3) fixation holes (n = 35), (4) three-piece PMMA optic-Prolene haptic (n = 50), (5) three-piece acrylic optic-PMMA haptic (n = 55), three-piece silicone optic with PMMA (6) or polyimide (7) haptics (n = 30), and (8) three-piece silicone optic-Prolene haptic (n = 80) lenses. TESTING: The eyes were sectioned in the equatorial plane for gross examination of the capsular bag from a posterior view. The cornea and iris were then excised for evaluation from an anterior view. MAIN OUTCOME MEASURES: ACO was scored in each eye from 0 to IV, according to the degree/area of capsule opacification. Capsulorrhexis size and IOL decentration were measured with calipers. RESULTS: The overall differences among the IOL groups regarding the three parameters were significant (ACO score: P < 0.001; capsulorrhexis diameter: P = 0.036; IOL decentration: P = 0.012). Mean ACO scores were highest with the large- and small-hole one-piece silicone-plate lenses (2.543 +/- 0.950) and lowest with the three-piece acrylic optic-PMMA haptic lenses (0.600 +/- 0.710). Of 10 cases of capsulorrhexis phimosis observed in the study, 7 cases were associated with three-piece silicone optic-Prolene haptic lenses, which also presented the highest mean decentration (0.375 +/- 0.601 mm). CONCLUSIONS: Our results confirm previous histopathologic observations that the rate of ACO is the lowest with acrylic lenses and higher with plate-haptic silicone IOLs. Nevertheless, clinical sequelae of capsular shrinkage are also very important with three-piece silicone optic-Prolene haptic designs. Thus, IOL material and design are significant factors in the development of ACO, but they ultimately also influence the clinical presentation of capsular shrinkage.

Acrylic Resins↗
PubMed2001

Effect of in-the-bag intraocular lens fixation on the prevention of posterior capsule opacification.

PURPOSE: To compare the incidence of posterior capsule opacification (PCO) after extracapsular cataract extraction (ECCE) and phacoemulsification and to evaluate the role of posterior chamber intraocular lens (PC IOL) haptic fixation and biomaterial/design in reducing the incidence. SETTING: Postgraduate Institute of Medical Education and Research, Chandigarh, India; Center for Research on Ocular Therapeutics and Biodevices, Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina, USA. METHODS: This study comprised 278 eyes of 263 patients having ECCE and 318 eyes of 297 patients having phacoemulsification with PC IOL implantation. Posterior capsule opacification leading to a decrease in Snellen visual acuity of 2 or more lines was considered visually significant. The presence of PCO and IOL haptic fixation were evaluated postoperatively using slitlamp biomicroscopy. Haptic position was noted as in-the-bag (B-B), 1 haptic in the bag and 1 in the sulcus (bag-sulcus [B-S]), or both haptics out of the bag (sulcus-sulcus [S-S]). In addition, the rate of visually significant PCO was compared among 3 IOL biomaterials: poly(methyl methacrylate), silicone, and hydrophobic acrylic. RESULTS: Visually significant PCO occurred in 42.45% of eyes having ECCE and 19.18% of eyes having phacoemulsification (P <.001, chi-square test) after a mean follow-up of 2.4 years +/- 0.7 (SD). In both groups, visually significant PCO was significantly less in eyes with B-B fixation than in those with B-S or S-S fixation (P <.001). The rate of visually significant PCO in all eyes in the phacoemulsification group with B-B fixation was low (11.90%) and was significantly lower in eyes with a hydrophobic acrylic IOL (2.22%; P <.05, chi-square test). CONCLUSIONS: In-the-bag PC IOL fixation is required to consistently reduce the incidence of PCO. Thorough removal of lens substance, including hydrodissection-assisted cortical cleanup, and in-the-bag PC IOL fixation seem to be the most important factors in reducing PCO, regardless of surgical procedure or IOL type used. Intraocular lens biomaterial and design also help prevent PCO.

Biocompatible Materials↗
PubMed2001

No-anesthesia clear corneal phacoemulsification versus topical and topical plus intracameral anesthesia. Randomized clinical trial.

PURPOSE: To compare the intraoperative pain scores during clear corneal phacoemulsification under no anesthesia, topical anesthesia, and topical plus intracameral anesthesia. SETTING: Dr. Agarwal's Eye Hospital and Eye Research Center, Chennai, India. METHODS: Seventy-five patients were randomized to have phacoemulsification under no anesthesia, topical anesthesia, or topical plus intracameral anesthesia. Uncooperative or illiterate patients and those with hard cataract, a shallow anterior chamber, or small pupils were excluded. A protocol was established for supplemental anesthesia in case of breakthrough pain during the surgery. Each patient was asked to grade the overall severity of intraoperative pain immediately after surgery on a 10-point visual analog scale. Also evaluated were the general discomfort during surgery, discomfort from the microscope lights, surgeon stress during surgery, and total surgical time. Comparison among the 3 groups was performed using an analysis of variance. RESULTS: No supplemental anesthesia was required in any group. No significant difference was noted in the mean scores of the subjective sensation of pain with or without topical anesthesia (P =.610). The mean scores of patient discomfort from the microscope lights and surgical time were also statistically insignificant. Patient discomfort and surgeon stress during surgery were significantly greater in the no-anesthesia group than in the topical and topical plus intracameral groups (P =.0235 and P = 0.0206, respectively). CONCLUSION: No-anesthesia clear corneal phacoemulsification was performed by a highly experienced, skilled surgeon without causing an unacceptable level of pain. However, this technique is not suitable for every cataract surgeon or patient.

Adult↗
PubMed2001

Dense opacification of the optical component of a hydrophilic acrylic intraocular lens: a clinicopathological analysis of 9 explanted lenses.

PURPOSE: To report clinical, pathological, histochemical, ultrastructural, and spectrographic analyses of explanted hydrophilic acrylic intraocular lenses (IOLs) obtained from patients who had visual disturbances caused by postoperative opacification of the lens optic. SETTING: Center for Research on Ocular Therapeutics and Biodevices, Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina, USA, and Ege University, Alsancak Izmir, Turkey. METHODS: Nine hydrophilic IOLs (SC60B-OUV, MDR Inc.) were explanted from 9 patients with decreased visual acuity. Most patients became symptomatic approximately 24 months after uneventful phacoemulsification and IOL implantation. Opacification was noted and appeared clinically to be associated with a fine granularity within the substance of the IOL optic. The IOLs were forwarded to the center and examined by gross and light microscopy. Full-thickness cut sections of the optics were stained with 1% alizarin red and the von Kossa method (special stains for calcium). Some were submitted for scanning electron microscopy and energy dispersive x-ray spectroscopy. RESULTS: Microscopic analyses revealed multiple fine, granular deposits of variable sizes within the lens optics, usually distributed in a line parallel to the anterior and posterior curvatures of the optic, with a clear zone just beneath the optic surface. The deposits stained positive with alizarin red and the von Kossa method. Energy dispersive x-ray spectroscopy of the internal substance of sectioned IOLs demonstrated the presence of calcium within the deposits. CONCLUSION: This is the first clinicopathological report of optic opacification occurring with this hydrophilic acrylic IOL model. Studies of similar cases with this lens should be done to determine the incidence and possible mechanisms of the phenomenon.

Acrylic Resins↗
PubMed2001

Effect of heparin surface modification in reducing silicone oil adherence to various intraocular lenses.

PURPOSE: To evaluate surface properties of various intraocular lenses (IOLs), including a newly fabricated heparin-surface-modified (HSM) silicone IOL, with special reference to their efficiency in reducing potential silicone oil adherence to the IOL optics. SETTING: Center for Research on Ocular Therapeutics and Biodevices, Department of Ophthalmology, Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina, USA. METHODS: Five groups of rigid and foldable IOLs were analyzed in an in vitro test for the percentage of silicone oil adherence: a single-piece foldable hydrophilic-acrylic IOL (n = 9); a single-piece rigid poly(methyl methacrylate) (PMMA) IOL with HSM coating of the lens optic (n = 9); a 3-piece foldable silicone optic IOL with HSM coating of the optic (n = 10); a single-piece standard rigid PMMA IOL (n = 7); and a standard 3-piece foldable silicone optic IOL (n = 9). After the IOLs were immersed in water and then in silicone oil, gross photographs taken. Image analysis was performed to evaluate the percentage of silicone oil coverage of the anterior and posterior surfaces of each IOL optic. RESULTS: The mean silicone oil coverage of the hydrophilic-acrylic IOLs was 5.6% +/- 2.5% (SD); of the HSM PMMA IOLs, 6.2% +/- 4.3%; of the HSM silicone optic IOLs, 6.7% +/- 3.2%; and of the standard PMMA IOLs, 20.3% +/- 13.3%. The mean silicone oil coverage was greatest on the standard silicone optic IOLs, 98.2% +/- 3.1%. CONCLUSIONS: Intraocular lenses with a hydrophilic optic have less tendency toward adherence to silicone oil than more hydrophobic designs. A foldable silicone IOL with heparin surface modification can significantly reduce potential silicone oil adherence, comparable to the level achievable with the rigid HSM PMMA designs. Two new foldable IOL styles, the HSM silicone IOL and IOLs in the general class of hydrophilic-acrylic, were highly efficacious in reducing silicone oil adherence. There is now a real choice of foldable lenses for patients with actual or potential vitreoretinal diseases.

Acrylic Resins↗
PubMed2001

3-D QSAR studies of triazolinone based balanced AT1/AT2 receptor antagonists.

Essential structural and physicochemical requirements in terms of common biophoric sites (pharmacophore) and secondary sites for binding and interacting with AT1 and AT2 receptors have been identified using APEX-3-D expert system on 16 N2- aryl triazolinone biphenyl sulphonamides. Among several biophoric 3-D QSAR models two models (Nos. 1 and 2) having R2 > 0.7, chance <0.05 and match >0.5 and two models (Nos. 3 and 4) having R2 > 0.89, chance <0.03 and match >0.5 with three biophoric sites and two secondary sites (except model No. 4 with three secondary sites) describe the variation in AT1 and AT2 antagonistic activities, respectively.

Angiotensin I↗
PubMed2001

Synthesis, molecular modeling and QSAR studies in chiral 2,3-disubstituted-1,2,3,4-tetrahydro-9H-pyrido(3,4-b)indoles as potential modulators of opioid antinociception.

In view of coexistence of opioid and cholecystokinin (CCK) in the brain areas concerned with pain processing, some semirigid racemic and chiral analogues of a potent CCK receptor antagonist (benzotript) have been synthesized and tested for their modulatory role on opioid antinociception, which may be mediated by CCK-B receptor. Some of these compounds, 3e, 3g, 3h, 4a, 4b and 4h, exhibited antinociceptive potentiation comparable to benzotript and proglumide. In order to identify the essential chemical structural features important for this potentiation, molecular modeling and quantitative structure activity relationship (QSAR) studies have been carried out in the S and R enantiomers of some of these semi-rigid compounds. The 3D-biophore models, common to all molecules of the training set have been derived. These models with superimposition (match value >0.25) depicted three biophoric sites one each for, pi/hydrophobic interactions, hydrogen bonding and ionic interactions among the phenyl/pyrrole ring, indole nitrogen, amidic oxygen, pyridyl nitrogen and lone pair of amidic oxygen. The total hydrophobicity and S absolute stereochemistry are found to positively contribute to potentiation of antinociception induced by morphine and the resulting quantitative pharmacophoric model with good correlation is found to well describe the observed activity.

Analgesics, Non-Narcotic↗
PubMed2001

Synthesis and QSAR studies in 2-(N-aryl-N-aroyl)amino-4,5-dihydrothiazole derivatives as potential antithrombotic agents.

A series of 2-(N-aryl-N-aroyl)amino-4,5-dihydrothiazole derivatives have been synthesized via cyclocondensation of N-aryl thioureas with 2-bromoethylamine hydrobromide followed by the reaction of the product thus obtained with aroyl chlorides. Title compounds were evaluated for their antithrombotic activity in vivo in mice where one of these compound 29 provided 65% protection as compared to 77% protection offered by the standard Indomethacin. Quantitative Structure-Activity Relationship (QSAR) studies were performed on these compounds using physicochemical (hydrophobic, electronic, steric) parameter as independent and antithrombic activity as dependent parameter, where antithrombotic activity correlated best (r > 0.8) with electronic parameters (F, sigma or mu) having high statistical significance > 99.9% (F(2,22)>15.0; F(2,22alpha:0.001)=11.0) suggesting that hydrophobic, steric and resonance factors are insignificant in this set of molecules for the activity.

Animals↗