Publications by authors named "Krishnan Raman"

17 Publications

  • Page 1 of 1

Liver Transplantation in Malaysia: Needs, Obstacles, and Opportunities.

Transplantation 2021 Dec;105(12):2507-2512

National Transplant Resource Centre, Ministry of Health, Kuala Lumpur, Malaysia.

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http://dx.doi.org/10.1097/TP.0000000000003591DOI Listing
December 2021

Berotralstat (BCX7353): Structure-Guided Design of a Potent, Selective, and Oral Plasma Kallikrein Inhibitor to Prevent Attacks of Hereditary Angioedema (HAE).

J Med Chem 2021 09 26;64(17):12453-12468. Epub 2021 Aug 26.

Hereditary angioedema (HAE) is a rare and potentially life-threatening disease that affects an estimated 1 in 50 000 individuals worldwide. Until recently, prophylactic HAE treatment options were limited to injectables, a burdensome administration route that has driven the need for an oral treatment. A substantial body of evidence has shown that potent and selective plasma kallikrein inhibitors that block the generation of bradykinin represent a promising approach for the treatment of HAE. Berotralstat (BCX7353, discovered by BioCryst Pharmaceuticals using a structure-guided drug design strategy) is a synthetic plasma kallikrein inhibitor that is potent and highly selective over other structurally related serine proteases. This once-daily, small-molecule drug is the first orally bioavailable prophylactic treatment for HAE attacks, having successfully completed a Phase III clinical trial (meeting its primary end point) and recently receiving the U.S. Food and Drug Administration's approval for the prophylactic treatment of HAE attacks in patients 12 years and older.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00511DOI Listing
September 2021

Impact of problematic internet use on the self-esteem of adolescents in the selected school, Kerala, India.

Arch Psychiatr Nurs 2020 06 10;34(3):122-128. Epub 2020 Feb 10.

Department of Psychiatry, Saveetha Medical College, Thandalam, Chennai, Tamil Nadu, India. Electronic address:

Background: Internet use is one of the essential tools of our present-day society whose impact is seen on adolescents such as increased use of the internet because they have free easy and daily access to the internet. Problematic internet use has become a global phenomenon that causes serious problem to the affected individual leading to impairment in psychological well-being.

Aim: The present study aims to assess the level of problematic internet use and self-esteem among adolescents in selected schools, Kochi, Kerala, India.

Setting: The study conducted in Private Aided School, in Kothamangalam Thaluk of Ernakulam Dist., Kerala.

Method: The study with the cross-sectional design was conducted for a period of one month among 60 students and participants were selected using non-probability, convenient sampling. The samples were provided with a self-administered questionnaire after obtaining written consent from their parents and the students.

Result: Karl-Pearson coefficient indicated a significant negative correlation between self-esteem and Internet addiction (r = -0.649 and p < 0.001).

Conclusion: The use of internet has been found to have a powerful impact on adolescents, especially in areas of self-esteem, and at times, it may affect their social life and relationship with the family.
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http://dx.doi.org/10.1016/j.apnu.2020.02.008DOI Listing
June 2020

Effectiveness of a Nurse-Led Intervention for Adolescents With Problematic Internet Use.

J Psychosoc Nurs Ment Health Serv 2020 Jul 12;58(7):16-26. Epub 2020 May 12.

The current study assessed the effect of an intervention on problematic internet use (PIU), biopsychosocial functioning, and academic performance in 100 adolescents with PIU in grades 9 and 11 in Ernakulam District, Kerala, India. Students from four comparable schools were randomly assigned to experimental and wait-list control groups after being screened for PIU. The experimental group participated in a 10-week intervention and parents of these adolescents were provided with two sessions. The wait-list control group received the intervention after the posttest. A PIU questionnaire, sociodemographic data, internet usage pattern, a biopsychosocial functioning tool, and academic performance were used to assess participants at baseline and immediately after and 3 months postintervention. Findings revealed significant differences in PIU; physical, psychological, and social functioning; and academic performance immediately and 3 months postintervention (p < 0.05). Thus, the intervention was effective in reducing PIU among adolescents and improved their physical, psychological, and social functioning and academic performance. [Journal of Psychosocial Nursing and Mental Health Services, 58(7), 16-26.].
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http://dx.doi.org/10.3928/02793695-20200506-03DOI Listing
July 2020

Outcomes of early versus delayed cholecystectomy in patients with mild to moderate acute biliary pancreatitis: A randomized prospective study.

Asian J Surg 2018 Jan 13;41(1):47-54. Epub 2016 Aug 13.

Hepatobiliary-Pancreatic Surgery Unit, Selayang Hospital, Lebuhraya Selayang-Kepong, 68100 Batu Caves, Selangor Darul Ehsan, Malaysia.

Background: In patients with acute biliary pancreatitis (ABP), cholecystectomy is mandatory to prevent further biliary events, but the precise timing of cholecystectomy for mild to moderate disease remain a subject of ongoing debate. The aim of this study is to assess the outcomes of early versus delayed cholecystectomy. We hypothesize that early cholecystectomy as compared to delayed cholecystectomy reduces recurrent biliary events without a higher peri-operative complication rate.

Methods: Patients with mild to moderate ABP were prospectively randomized to either an early cholecystectomy versus a delayed cholecystectomy group. Recurrent biliary events, peri-operative complications, conversion rate, length of surgery and total hospital length of stay between the two groups were evaluated.

Results: A total of 72 patients were enrolled at a single public hospital. Of them, 38 were randomized to the early group and 34 patients to the delayed group. There were no differences regarding peri-operative complications (7.78% vs 11.76%; p = 0.700), conversion rate to open surgery (10.53% vs 11.76%; p = 1.000) and duration of surgery performed (80 vs 85 minutes, p = 0.752). Nevertheless, a greater rate of recurrent biliary events was found in the delayed group (44.12% vs 0%; p ≤ 0.0001) and the hospital length of stay was longer in the delayed group (9 vs 8 days, p = 0.002).

Conclusion: In mild to moderate ABP, early laparoscopic cholecystectomy reduces the risk of recurrent biliary events without an increase in operative difficulty or perioperative morbidity.
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http://dx.doi.org/10.1016/j.asjsur.2016.07.010DOI Listing
January 2018

A rare case modafinil dependence.

J Pharmacol Pharmacother 2015 Jan-Mar;6(1):49-50

Department of Pharmacology, Saveetha Medical College, Chennai, Tamil Nadu, India.

Modafinil, a non-amphetamine psychostimulant, is indicated for narcolepsy, shift work sleep disorder and severe obstructive sleep apnea syndrome. Modafinil is prescribed at the dose of 100 mg once in a day or as two doses, 12 h apart in a day. It has also been found that it reduces cocaine dependence and withdrawal phenomenon. Modafinil is claimed to have very low liability for abuse and dependence. Here we report a rare case of modafinil dependence.
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http://dx.doi.org/10.4103/0976-500X.149149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4319252PMC
February 2015

ADad 4: the symptomatology and clinical presentation of Anxiety Disorders among adolescents in a rural community population in India.

Indian J Pediatr 2013 Nov 24;80 Suppl 2:S149-54. Epub 2013 Sep 24.

Child Development Centre, Thiruvananthapuram Medical College, Thiruvananthapuram, 695 011, Kerala, South India,

Objectives: Anxiety Disorders (AD) in children and adolescents present with unique clinical features and exhibit phenotypic diversity. The symptom presentation varies with regard to age of onset, developmental factors and gender. This study documents the clinical presentation of AD among adolescents in India, and explores the symptom clusters among the different age groups as well as gender.

Methods: Five hundred adolescents aged between 11 and 19 y from Pattanakad ICDS block, of Allapuzha district in Kerala were recruited and assessed using the self-rated Screen for Child Anxiety Related Emotional Disorders (SCARED) questionnaire to identify symptom clusters of anxiety and this was followed by confirmation of the diagnosis using DSM-IV TR within a week. Anxiety symptom clusters and severity (obtained from continuous SCARED scores) were compared between early, middle and late adolescence subgroups as well as between sexes.

Results: The most predominant anxiety symptoms across the subtypes were the anxious mood, which was noted in 12.60% followed by cognitive symptoms in 9.94% of the cases and finally physical symptoms in 9.22% of the study sample. The symptom clusters varied among the subtypes with anxious mood being commoner in Panic Disorder (PD), cognitive symptoms in Generalised Anxiety Disorder (GAD) and physical symptoms were prominent among Separation Anxiety (SeAD) and Social Anxiety Disorders (SoAD). The severity of anxiety disorder in general and its various subtypes were mostly of mild intensity although significant proportion had a severe form of the disease(s). The severity of the AD among girls was statistically significantly higher than boys (P = 0.02). There was no significant difference on symptom frequency or anxiety severity with regard to age.

Conclusions: Understanding of age appropriate presentation of anxiety symptoms may help in streamlining the treatment guidelines and yield a better estimate of the disease process.
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http://dx.doi.org/10.1007/s12098-013-1234-1DOI Listing
November 2013

ADad 3: the epidemiology of Anxiety Disorders among adolescents in a rural community population in India.

Indian J Pediatr 2013 Nov 18;80 Suppl 2:S144-8. Epub 2013 Sep 18.

Child Development Centre, Thiruvananthapuram Medical College, Thiruvananthapuram, 695 011, Kerala, South India,

Objectives: Despite being the most common mental health concern, there is paucity of literature on the epidemiology of anxiety disorders among the adolescent population in India. This study aimed to estimate the period prevalence of Anxiety Disorders (AD) among 11 to 19 y old adolescents in India.

Methods: A representative sample of adolescents (N = 500) from a rural community in Southern India was assessed for the period prevalence of all and specific Anxiety Disorders using Screen for Child Anxiety Related Emotional Disorders (SCARED), and confirmed in a subsequent interview with Schedule for Affective Disorders and Schizophrenia for School-Age Children/Present and Lifetime Version (K-SADS-PL).

Results: The prevalence for all AD using the international, Indian SCARED cut-offs and DSM-IV-TR criteria was 8.6 % (boys = 2%; girls = 6.6%), 25.8% (boys = 6.6%; girls = 19.2%) and 14.4 % (boys = 4.8%; girls = 9.6%) respectively. There were significant gender differences in the prevalence for all Anxiety Disorders (χ (2) = 3.61, df = 1; P < 0.05), Separation Anxiety Disorder (χ (2) = 22.27, df = 1; P < 0.001) and Social Anxiety Disorder (χ(2) = 4.29, df = 1; P < 0.03). Significant age difference in the prevalence of Panic Disorder (χ(2) = 10.32; df = 1; P = 0.00) and Generalized Anxiety Disorder (χ(2) = 5.87; df = 1; P = 0.05) was noted.

Conclusions: The prevalence of Anxiety Disorders in South Indian adolescents was higher than found in the western literature. Prevalence of specific AD was age and gender specific. Adolescent and mental health policies must integrate anxiety disorder of public health significance.
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http://dx.doi.org/10.1007/s12098-013-1097-5DOI Listing
November 2013

Neuroendocrine tumor in choledochal cyst--case report and review of literature.

Pol Przegl Chir 2011 Nov;83(11):627-9

Department of HPB Surgery, Hospital Selayang, Lebuhraya Selayang-Kepong, Batu Caves, Selangor Darul Ehsan, Malaysia.

The report presents a rare case of carcinoid tumor in a 17 year female who presented with epigastric pain of one week duration. She was diagnosed to have type I choledochal cyst on abdominal ultrasound and MRI. She underwent total excision of choledochal cyst with roux-en-Y hepaticojejunostomy. Histopathological examination revealed a neuroendocrine tumor within choledochal cyst which was immunoreactive for Chromogranin A. Patient is well at 6 months of follow up. These tumors are characteristically slow-growing, therefore awareness of its presence preoperatively can facilitate optimal management by performing surgical resection with negative margins which offers the best chance of long-term survival.
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http://dx.doi.org/10.2478/v10035-011-0099-0DOI Listing
November 2011

A rare complication of endoscopic cystgastrostomy.

Gastroenterology 2011 Nov 23;141(5):e1-2. Epub 2011 Sep 23.

Department of Hepatology, Hospital Selayang, Selangor, Malaysia.

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http://dx.doi.org/10.1053/j.gastro.2010.07.062DOI Listing
November 2011

Cystic pheochromocytoma mimicking a malignant pancreatic cyst.

Gastrointest Endosc 2011 Sep 15;74(3):712-3. Epub 2010 Dec 15.

Department of Hepatology, Hospital Selayang, Selangor, Malaysia.

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http://dx.doi.org/10.1016/j.gie.2010.09.027DOI Listing
September 2011

Pancreatic hemangioma mimicking a malignant pancreatic cyst.

Gastrointest Endosc 2011 Jan 8;73(1):174-6. Epub 2010 Oct 8.

Department of Hepatology, Hospital Selayang, Kuala Lumpur, Malaysia.

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http://dx.doi.org/10.1016/j.gie.2010.07.038DOI Listing
January 2011

Design, parallel synthesis, and crystal structures of biphenyl antithrombotics as selective inhibitors of tissue factor FVIIa complex. Part 1: Exploration of S2 pocket pharmacophores.

Bioorg Med Chem 2009 Jun 12;17(11):3934-58. Epub 2009 Apr 12.

BioCryst Pharmaceuticals, Inc., 2190 Parkway Lake Drive, Birmingham, AL 35244, USA.

Factor VIIa (FVIIa), a serine protease enzyme, coupled with tissue factor (TF) plays an important role in a number of thrombosis-related disorders. Inhibition of TF x FVIIa occurs early in the coagulation cascade and might provide some safety advantages over other related enzymes. We report here a novel series of substituted biphenyl derivatives that are highly potent and selective TF x FVIIa inhibitors. Parallel synthesis coupled with structure-based drug design allowed us to explore the S2 pocket of the enzyme active site. A number of compounds with IC(50) value of <10 nM were synthesized. The X-ray crystal structures of some of these compounds complexed with TF x FVIIa were determined and results were applied to design the next round of inhibitors. All the potent inhibitors were tested for inhibition against a panel of related enzymes and selectivity of 17,600 over thrombin, 450 over trypsin, 685 over FXa, and 76 over plasmin was achieved. Two groups, vinyl 36b and 2-furan 36ab, were identified as the optimum binding substituents on the phenyl ring in the S2 pocket. Compounds with these two substituents are the most potent compounds in this series with good selectivity over related serine proteases. These compounds will be further explored for structure-activity relationship.
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http://dx.doi.org/10.1016/j.bmc.2009.04.013DOI Listing
June 2009

Crystal structure of vaccinia virus uracil-DNA glycosylase reveals dimeric assembly.

BMC Struct Biol 2007 Jul 2;7:45. Epub 2007 Jul 2.

Center for Biophysical Sciences & Engineering, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

Background: Uracil-DNA glycosylases (UDGs) catalyze excision of uracil from DNA. Vaccinia virus, which is the prototype of poxviruses, encodes a UDG (vvUDG) that is significantly different from the UDGs of other organisms in primary, secondary and tertiary structure and characteristic motifs. It adopted a novel catalysis-independent role in DNA replication that involves interaction with a viral protein, A20, to form the processivity factor. UDG:A20 association is essential for assembling of the processive DNA polymerase complex. The structure of the protein must have provisions for such interactions with A20. This paper provides the first glimpse into the structure of a poxvirus UDG.

Results: Results of dynamic light scattering experiments and native size exclusion chromatography showed that vvUDG is a dimer in solution. The dimeric assembly is also maintained in two crystal forms. The core of vvUDG is reasonably well conserved but the structure contains one additional beta-sheet at each terminus. A glycerol molecule is found in the active site of the enzyme in both crystal forms. Interaction of this glycerol molecule with the protein possibly mimics the enzyme-substrate (uracil) interactions.

Conclusion: The crystal structures reveal several distinctive features of vvUDG. The new structural features may have evolved for adopting novel functions in the replication machinery of poxviruses. The mode of interaction between the subunits in the dimers suggests a possible model for binding to its partner and the nature of the processivity factor in the polymerase complex.
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http://dx.doi.org/10.1186/1472-6807-7-45DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1936997PMC
July 2007

Probing the S2 site of factor VIIa to generate potent and selective inhibitors: the structure of BCX-3607 in complex with tissue factor-factor VIIa.

Acta Crystallogr D Biol Crystallogr 2007 Jun 15;63(Pt 6):689-97. Epub 2007 May 15.

BioCryst Pharmaceuticals, 2190 Parkway Lake Drive, Birmingham, AL 35216, USA.

Factor VIIa (FVIIa) is a trypsin-like serine protease in the coagulation cascade. Its complex with tissue factor (TF) triggers the extrinsic pathway of the coagulation cascade, generating a blood clot. Research programs at several centers now recognize the important roles played by TF and FVIIa in both the thrombotic and inflammatory processes associated with cardiovascular diseases. Therefore, inhibition of the TF-FVIIa complex is seen as a promising target that is key to the development of clinical candidates for various cardiovascular applications. The crystal structure of the TF-FVIIa enzyme complex has been analyzed in order to design and synthesize small-molecule inhibitors. Using structure-based drug design (SBDD), a new series of inhibitors have been discovered that demonstrate high potency against the TF-FVIIa complex while maintaining substantial selectivity versus other closely related serine proteases such as trypsin, thrombin, factor Xa and plasmin.
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http://dx.doi.org/10.1107/S0907444907014187DOI Listing
June 2007

Mechanisms of Arg-Pro-Pro-Gly-Phe inhibition of thrombin.

Am J Physiol Heart Circ Physiol 2003 Jul 21;285(1):H183-93. Epub 2003 Feb 21.

Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-0640, USA.

Investigations determined the mechanism(s) by which Arg-Pro-Pro-Gly-Phe (RPPGF) inhibits thrombin-induced platelet activation. High concentrations of RPPGF inhibit thrombin-induced coagulant activity. RPPGF binds to the active site of thrombin by forming a parallel beta-strand with Ser214-Gly216 and interacts with His57, Asp189, and Ser195 of the catalytic triad. RPPGF competitively inhibits alpha-thrombin from hydrolyzing Sar-Pro-Arg-paranitroanilide with a Ki = 1.75 +/- 0.03 mM. Other mechanisms were sought to explain why RPPGF inhibits thrombin activation of platelets at concentrations below that which inhibits its active site. Soluble RPPGF blocks biotinylated NATLDPRSFLLR of the thrombin cleavage site on protease-activated receptor (PAR)1 from binding to the peptide RPPGC (IC50 = 20 microM). The soluble recombinant extracellular domain of PAR1 (rPAR1EC) blocks biotinylated RPPGF binding to rPAR1EC (IC50 = 50 microM) bound to microtiter plates, but rPAR1EC deletion mutants missing the sequence LDPR or PRSF do not. RPPGF and related forms prevent the thrombin-like enzyme thrombocytin from proteolyzing rPAR1EC at concentrations that do not block thrombocytin's active site. These studies indicate that RPPGF is a bifunctional inhibitor of thrombin: it binds to PAR1 to prevent thrombin cleavage at Arg41 and interacts with the active site of alpha-thrombin.
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http://dx.doi.org/10.1152/ajpheart.00490.2002DOI Listing
July 2003
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