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1.
Int J Trichology ; 15(1): 13-17, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37305189

RESUMEN

Topical minoxidil is used for treating different hair disorders. Even though it is an effective therapy, many patients show poor compliance due to the cost, side effects, and duration of treatment. Topical minoxidil is the mainstay treatment for androgenetic alopecia (AGA). Recently, low alcohol or alcohol-free topical minoxidil formulation has proven to be an alternative for patients suffering from AGA, including those with poor compliance with other therapies. Thus, the current article provides the positioning of low alcohol or alcohol-free topical minoxidil to manage AGA in Indian clinical practice.

2.
Ceylon Med J ; 65(4): 86-94, 2020 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-34821487

RESUMEN

INTRODUCTION: Poor sleep quality have been reported among adults in most countries and are increasingly been reported in their predecessors, the college students. The present study aimed to assess sleep patterns and determine its association with various correlates amongst college students for effective and timely interventions in the habit-forming years of the life. METHODOLOGY: This was a cross sectional study done among college students enrolled in different courses, in Rishikesh municipal corporation area, in Dehradun district of Uttarakhand, India. Sleep Quality was assessed using a validated Pittsburgh Sleep Quality Index (PSQI), which has seven components while Perceived Stress Scale-10 assessed Stress. RESULTS: Poor sleep quality was reported among 66% of respondents. Mean sleep latency among respondents was 27.2 minutes (SD 20.75 min), with a median and mode of 20 minutes and 60 minutes respectively.On logistic regression analysis, yoga/ meditation, which have been recognized as effective relaxation techniques since ages, were found to have a positive association with better sleep quality (OR 0.47, 95% CI (0.26 - 0.84). Stress (OR 4.10, 95% CI 1.71- 9.83) and mobile use before bedtime (OR 1.956, 95% CI: 1.02- 3.75) were also significant predictors of poor sleep quality. CONCLUSIONS AND RECOMMENDATIONS: The prevalence of poor sleep quality was quite high. Relaxation techniques such as yoga/ meditation and stress relieving workshops may pay rich dividends. Use of electronic devices before bedtime need to be restricted for better sleep quality.


Asunto(s)
Trastornos del Inicio y del Mantenimiento del Sueño , Sueño , Adulto , Estudios Transversales , Humanos , India/epidemiología , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Trastornos del Inicio y del Mantenimiento del Sueño/terapia , Estudiantes
3.
Surg Neurol Int ; 10: 142, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31528477

RESUMEN

BACKGROUND: Cranioplasty is the surgical intervention to repair cranial defects in both cosmetic and functional ways. Despite the fact that cranioplasty is a simple procedure, it is still associated with a relatively high complication rate, ranging between series from 12% to 50%. METHODS: The author did a prospective cohort study of patients from August 2015 to December 2017, who had undergone decompressive craniectomy followed by cranioplasty after 6 weeks at our institution. All patients were followed up to 6 months after cranioplasty and complications were recorded both by imaging and clinically. The complications were classified as minor (subgaleal collection, seizures) who did not require the second surgery and major (hydrocephalus, bone flap infection) who required the second surgery. To find out neurological outcome, Glasgow coma score (GCS) and Glasgow outcome scale extended (GOSE) were recorded at 1 month, 3 months, and 6 months. RESULTS: Overall complication rate in this study was 22.4% (16/72). Subgaleal collection was the most common complication (5.6%), followed by hydrocephalus (4.2%), seizure (4.2%), bone flap infection (2.8%), intracerebral hematoma (2.8%), empyema (1.4%), and subdural hematoma (SDH) (1.4%). Of these, 8.4% (n = 6/72) were major complication (hydrocephalus n = 3, bone flap infection n = 2, and SDH n = 1) which required the second surgery. GCS and GOSE were assessed preoperatively and in postoperative period at 1 month, 3 months, and 6 months. Both mean values of GCS and GOSE showed a significant improvement at 3 and 6 months after cranioplasty. CONCLUSION: Cranioplasty after decompressive craniectomy is associated with higher complication rate, but good neurological outcome after surgery always outweighs the complications. KEY MESSAGE: Cranioplasty after decompressive craniectomy is associated with higher complication rate, but good neurological outcome after surgery always outweighs the complications. However, complications rate can be brought down by meticulous timing of cranioplasty in a patient of well-controlled comorbidities and precise surgical techniques. However, storing bone in bone bank is not an additional factor for any postcranioplasty complications which was considered previously.

4.
Surg Neurol Int ; 9: 80, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29721358

RESUMEN

BACKGROUND: Among various locations of intracranial aneurysms reported in the literature, two different aneurysms situated symmetrically opposite on bilateral distal anterior cerebral arteries (DACA) are very rare. CASE DESCRIPTION: Here, we report a rare case of mirror image distal anterior cerebral aneurysm in a middle-aged male patient. The patient presented with severe headache and loss of consciousness. Angiography was done which suggested mirror imaging of two aneurysms located over both DACA. It was treated through microsurgical approach with a successful outcome. CONCLUSION: Careful analysis of intracranial vasculature should be done using angiography, particularly in different views and stages to rule out multiple aneurysms at different locations in the same artery or at different arteries. Mirror images of bilateral DACA aneurysms are very rare. Fundamental surgical strategy of securing the parent artery and clipping the neck after meticulous dissection should be followed.

5.
Childs Nerv Syst ; 34(8): 1589-1592, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29556696

RESUMEN

PURPOSE: Purely cystic brain stem epidermoid is a rare diagnosis among all brainstem cystic lesions. Further, it is very rare in pediatric age group. METHODS: Here, we are reporting a rare case of completely cystic brain stem epidermoid in a child. The patient presented with clinical features of brain stem involvement. MRI brain was suggestive of cystic brain stem lesion. RESULTS: Patient went through surgical procedure. Final diagnosis of epidermoid cyst was confirmed on histopathological report. CONCLUSION: With the help of various advanced sequences of MRI like diffusion and ADC, diagnosis of epidermoid cyst can be established at unusual intracranial site also. Surgical resection of epidermoid cyst at brain stem should be attempted judiciously utilizing all modern tools of neurosurgery.


Asunto(s)
Tronco Encefálico/diagnóstico por imagen , Tronco Encefálico/cirugía , Quiste Epidérmico/diagnóstico por imagen , Quiste Epidérmico/cirugía , Preescolar , Femenino , Humanos
6.
Surg Neurol Int ; 9: 249, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30603233

RESUMEN

BACKGROUND: Primary orbital lymphomas are a rare subset of tumors constituting 1-2% of non-Hodgkin's lymphoma. They are mostly indolent B-cell lymphomas presenting with gradual progressive proptosis, decreased visual acuity, restricted ocular mobility, and diplopia. The role of surgery is mainly for obtaining a biopsy. Most of these tumors require multimodality treatment including chemotherapy, radiation, or both, which have major role. CASE DESCRIPTION: We report one such case of marginal zone lymphoma of the orbit in a female with significant proptosis who was treated with multimodality treatment, including surgical excision as a major treatment modality. Decompression of symptomatic proptosis was followed by chemotherapy and radiation. CONCLUSION: Primary orbital lymphoma is a rare clinical entity with diverse clinical outcomes. It can be successfully managed with surgical excision for decompression of mechanical proptosis followed by chemotherapy, radiation, or both.

7.
Int J Clin Pediatr Dent ; 10(2): 126-130, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28890610

RESUMEN

BACKGROUND: Early childhood caries discloses a distinct clinical pattern, and the teeth most often involved are the maxillary central incisors, lateral incisors, and the maxillary and man-dibular first molars. The maxillary incisors are most severely affected, with deep carious lesions usually involving the pulp. Teeth that have been endodontically treated often have little coronal tooth tissue remaining and as such require a post to retain the core and restoration .This study evaluated and compared the efficacy of EverStick glass fiber-reinforced composite post with ParaPost Taper Lux in primary maxillary anterior teeth. AIM: An in vivo study was conducted to evaluate and compare the longevity and failures of two fiber post systems in primary maxillary anterior teeth. MATERIALS AND METHODS: A total of 60 severely mutilated primary maxillary anterior teeth from children aged 3 to 5 years were selected according to the inclusion criteria. These teeth were treated endodontically and were randomly assigned into two groups with 30 samples in each group, group I: EverStick glass fiber-reinforced composite post, group II: ParaPost Taper Lux post. The evaluation of dislodgment of posts, secondary caries, root fracture, and post fracture was carried out clinically and radiographically during every follow-up at 3, 6, 9, and 12 months interval. RESULTS: Statistical tests (Chi-square test, Fisher's exact probability test) suggested that dislodgment of the posts was significant between the two groups at 6, 9, and 12 months follow-ups. But within the group during subsequent follow-up intervals, dislodgment of posts as a mode of failure was not statistically significant. However, clinically failures were seen in both the study groups. CONCLUSION: Fiber post system has proved to be successful clinically in both primary and permanent teeth due to the mono-block effect with luting agent, post system, core material, and bonding to dentin. Thus, today the EverStick glass fiber post system provides a novel way of fabricating cost-effective and less time-consuming custom-made post in treating mutilated maxillary anteriors. HOW TO CITE THIS ARTICLE: Sawant A, Chunawalla Y, Morawala A, Kanchan NS, Jain K, Talathi R. Evaluation of Novel Glass Fiber-reinforced Composite Technique for Primary Anterior Teeth with Deep Carious Lesions: A 12-month Clinical Study. Int J Clin Pediatr Dent 2017;10(2):126-130.

8.
Asian J Neurosurg ; 11(2): 176-7, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27057236

RESUMEN

Neurocysticercosis (NCC) is a parasitic infestation of the central nervous system. NCC parasitic infestation can be misdiagnosed as hydatid cyst or intraventricular epidermoid cyst that can cause a diagnostic dilemma. A 23-year-old male patient presented with headache and vomiting for 3-4 days and giddiness for 4-5 days. Magnetic resonance imaging with contrast was suggestive of a rim-enhancing lesion at the level of the foramen of Monro. Endoscopic excision of the lesion was done, and the patient had relief of a headache and vomiting immediately after the procedure. He is being followed up regularly. Intraventricular NCC occluding both foramen of Monro is a rare entity. Complete endoscopic surgical excision followed by appropriate drug therapy should be given to achieve a cure.

9.
J Med Chem ; 59(6): 2381-95, 2016 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-26859603

RESUMEN

Opioid receptor screening of a conopeptide library led to a novel selective κ-opioid agonist peptide (conorphin T). Intensive medicinal chemistry, guided by potency, selectivity, and stability assays generated a pharmacophore model supporting rational design of highly potent and selective κ-opioid receptor (KOR) agonists (conorphins) with exceptional plasma stability. Conorphins are defined by a hydrophobic benzoprolyl moiety, a double arginine sequence, a spacer amino acid followed by a hydrophobic residue and a C-terminal vicinal disulfide moiety. The pharmacophore model was supported by computational docking studies, revealing receptor-ligand interactions similar to KOR agonist dynorphin A (1-8). A conorphin agonist inhibited colonic nociceptors in a mouse tissue model of chronic visceral hypersensitivity, suggesting the potential of KOR agonists for the treatment of chronic abdominal pain. This new conorphine KOR agonist class and pharmacophore model provide opportunities for future rational drug development and probes for exploring the role of the κ-opioid receptor.


Asunto(s)
Analgésicos/farmacología , Caracol Conus/química , Dinorfinas/farmacología , Receptores Opioides kappa/agonistas , Dolor Abdominal/tratamiento farmacológico , Animales , Células CHO , Cricetinae , Cricetulus , AMP Cíclico/biosíntesis , Ensayos Analíticos de Alto Rendimiento , Hipersensibilidad/tratamiento farmacológico , Masculino , Ratones , Ratones Endogámicos C57BL , Simulación del Acoplamiento Molecular , Neuronas Aferentes/efectos de los fármacos , Biblioteca de Péptidos , Ratas , Ratas Wistar , Relación Estructura-Actividad
10.
J Clin Diagn Res ; 9(3): ZC48-52, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25954705

RESUMEN

BACKGROUND: Bone grafting is a dynamic phenomenon. It is a surgical procedure that replaces missing bone with material either from patient's own body, or, an artificial, synthetic or natural substitute. A successful bone graft when applied, heals, becomes incorporated, re-vascularises and eventually assumes the form desired. AIMS AND OBJECTIVE: The main purpose of this present study was to radiologically assess and compare the regenerative potential of hydroxyapatite with Collagen (G-Graft) and hydroxyapatite (G-Bone) and to evaluate the clinical usefulness of these materials to enhance bone healing in third molar extraction sites through bone formation. MATERIALS AND METHODS: The study was carried out in the Department of Oral & Maxillofacilal Surgery, patients were divided into three groups. The rationale for assigning the patients to the groups was strictly random: Group I - G-Graft (Hydroxyapatite with Collagen) was used as Bone graft material, Group II - Bone graft material used was G-Bone (Hydroxyapatite), Group III-control group (no grafts was used). Orthopentomogram(OPG) images were taken intra-operatively, just after extraction in the Group III (control), after extraction but before graft placement in Group I & II (study groups) and post-operatively at the end of first month and third month. Bone density of the post-extraction sockets was measured at four random areas through 'densitometric analysis' software in the OPG program (Kodak 8000C Digital Panoramic System, Eastman Kodak Company) and an average value was recorded at each review. RESULTS: The percentage increase in bone density between 1(st) month & 3(rd) month was 7.55± 12.43 in Group I (G Graft), 4.41± 5.4859 in Group II (G Bone), while that Group III (control) was found to be -0.82 ± 3.96. The bone density increase was found to be statistically highly significant (p<0.01)) between all groups. CONCLUSION: The present study concluded that G-Graft has a definite regenerative potential and is better than G-bone and can be used in bony defects to enhance the bone healing without provoking any significant inflammatory process. The study also indicates that defects treated with G-Graft attain more density initially and that G-Graft enhances bone healing in early stage.

11.
J Indian Soc Periodontol ; 18(5): 648-50, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25425830

RESUMEN

The replacement of missing teeth with implant-borne restorations has become a treatment modality accepted by the scientific community for fully and partially edentulous patients. Recent reports have demonstrated the successful placement of dental implants into the fresh extraction socket in the anterior as well as in molar regions, which is made possible due to modification in implant surface. The present case report highlights the placement of three bicortical screw (BCS) implants into the fresh extraction sockets and one KOS implant in edentulous area with flapless technique. All the implants were immediately loaded and followed up for a period of 6 months.

12.
N Y State Dent J ; 80(6): 38-42, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25675614

RESUMEN

UNLABELLED: Diabetes mellitus (DM) is undiagnosed in approximately half of the patients actually suffering from the disease. In addition, the prevalence of DM is more than twice as high as in patients with periodontitis when compared to periodontally healthy subjects. Thus, a high number of patients with periodontitis may have undiagnosed DM. The purpose of the present study was to evaluate whether blood oozing from a gingival crevice during routine periodontal examination can be used for determining glucose levels. MATERIALS AND METHODS: Observational cross-sectional studies were carried out in 75 patients (43 males and 32 females) with chronic periodontitis who were divided into two groups: Group I and Group II, respectively. Blood oozing from the gingival crevices of anterior teeth following periodontal probing was collected with the stick of glucose self-monitoring device, and the blood glucose levels were measured. At the same time, finger-prick blood was taken for glucometric analysis and subsequent readings were recorded. RESULTS: The patient's blood glucose values ranged from 74 to 256 mg/dl. The comparison between gingival crevicular blood and finger-prick blood showed a very strong correlation, with a t value of 3.97 (at P value = 0.001). CONCLUSIONS: The data from this study has shown that GCB collected during diagnostic periodontal examination can be an excellent source of blood for glucometric analysis.


Asunto(s)
Glucemia/análisis , Periodontitis Crónica/sangre , Líquido del Surco Gingival/química , Automonitorización de la Glucosa Sanguínea/instrumentación , Capilares , Estudios Transversales , Diabetes Mellitus/sangre , Estudios de Factibilidad , Femenino , Dedos/irrigación sanguínea , Hemorragia Gingival/sangre , Humanos , Masculino , Reproducibilidad de los Resultados
13.
J Investig Clin Dent ; 4(2): 84-8, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23073970

RESUMEN

OBJECTIVE: Recent studies suggest that chronic periodontitis can lead to a decrease in levels of red blood cell (RBC) and hemoglobin concentration. Smoking is an established risk factor for periodontitis. The present study was carried out to evaluate the effect of cigarette smoking on the various parameters of RBC in the subjects with chronic periodontitis. METHODS: A total of 77 males with chronic periodontitis were divided into 38 nonsmokers (group I) and 39 current smokers (group II). Clinical parameters recorded were probing pocket depth and clinical attachment level. Laboratory blood investigations included hemoglobin concentration, RBC count, packed cell volume, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration and erythrocyte sedimentation rate. RESULTS: In group II probing pocket depth and clinical attachment level and erythrocyte sedimentation rate were significantly higher than in group I. The RBC count, hemoglobin concentration, and packed cell volume were significantly lower in group II compared to group I. While the mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration were comparable in both the groups. CONCLUSION: Smoking may have an effect on levels of various RBC parameters in patients with chronic periodontitis.


Asunto(s)
Periodontitis Crónica/sangre , Eritrocitos/patología , Fumar/efectos adversos , Fumar/sangre , Adulto , Sedimentación Sanguínea , Periodontitis Crónica/etiología , Recuento de Eritrocitos , Índices de Eritrocitos , Eritrocitos/química , Hematócrito , Humanos , Masculino , Persona de Mediana Edad
14.
Indian J Gastroenterol ; 31(4): 165-70, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22886321

RESUMEN

BACKGROUND AND AIMS: This study aimed to evaluate the prevalence of low bone mineral density (BMD) in recently diagnosed adult celiac patients and to identify the factors associated with this. METHODS: We investigated 54 newly diagnosed adult celiac patients between February 2008 and April 2009. BMD was measured in all patients and its correlation with clinical and biochemical parameters was analyzed. RESULTS: Fifty-four (24 male) newly diagnosed celiac patients with a mean±SD age of 30.6 ± 9.3 years (range 18-50) were included. Thirty-nine (72.2 %) presented with intestinal symptoms, and the rest with extraintestinal symptoms. Low vitamin D levels were seen in 11 (20.3 %) patients and elevated iPTH (secondary hyperparathyroidism) in 12 (22.2 %) patients. Twenty-one (39 %) patients had normal BMD, 23 (43 %) had osteopenia (T-score -1 to -2.5), and 10 (18 %) patients had osteoporosis (T-score <-2.5). A statistically significant association was seen between BMD and age of onset, duration of illness, serum tTGA levels, serum vitamin D levels, and histopathological changes. CONCLUSIONS: Low BMD is common in newly diagnosed adult celiac patients with approximately one fifth of them having osteoporosis. BMD should be measured in all newly diagnosed celiac patients and calcium and vitamin D supplementation included in the treatment regimen.


Asunto(s)
Densidad Ósea , Huesos/metabolismo , Enfermedad Celíaca/metabolismo , Vitamina D/sangre , Absorciometría de Fotón , Adolescente , Adulto , Huesos/diagnóstico por imagen , Enfermedad Celíaca/diagnóstico por imagen , Femenino , Humanos , Hiperparatiroidismo Secundario/complicaciones , Hiperparatiroidismo Secundario/diagnóstico , Masculino , Persona de Mediana Edad , Osteoporosis/complicaciones , Osteoporosis/diagnóstico por imagen , Hormona Paratiroidea/sangre , Prevalencia , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/diagnóstico , Adulto Joven
15.
Indian J Gastroenterol ; 31(3): 116-20, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22717947

RESUMEN

BACKGROUND: Celiac disease (CD) is being increasingly recognized in adults though a majority of patients continue to be diagnosed in childhood. AIM: To compare the clinical presentation and profile of newly diagnosed pediatric and adolescent/adult CD patients. MATERIALS AND METHODS: Retrospective analysis of patients diagnosed with CD between year 1997 and 2007 in the pediatric group, and between year 2000 and 2007 in the adolescent/adult group was done for clinical presentation, endoscopic findings and duodenal histology. RESULTS: A total of 434 children and 298 adults were studied. The mean age of diagnosis was 6.5 ± 2.5 years (1-11 years) in children and 29.3 ± 13.3 years (6-73 years) in adolescent/adults. The mean duration of symptoms before diagnosis was 3.5 ± 2.5 years in children and 4.9 ± 4.6 years in the latter. Diarrhea as the presenting symptom was seen in 74 % of children and 58.7 % of adolescent/adults. Anemia (on investigations) was seen in 84 % of children and 94 % of adolescent/adults. CONCLUSIONS: Pediatric patients of CD present more often with typical features than adults. Atypical presentations are more common in adults and the latent period for diagnosis is also longer in adolescent/adults. There is a need for increasing awareness about CD, both among pediatricians and physicians caring for adult patients.


Asunto(s)
Enfermedad Celíaca/complicaciones , Adolescente , Adulto , Anciano , Anemia/etiología , Anemia/patología , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/patología , Niño , Preescolar , Diarrea/etiología , Diarrea/patología , Femenino , Humanos , India , Lactante , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Atención Terciaria de Salud , Adulto Joven
16.
J Gastrointest Cancer ; 43(2): 267-71, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21573879

RESUMEN

PURPOSE: Gallbladder and pancreas share common embryological origin, and malignancies of these organs may share common tumor antigens. CA 242 is a tumor marker for pancreatic cancer, but has not been studied in gallbladder cancer (GBC). We measured serum CA 242 levels in patients with GBC and compared it with those in patients with gallstones (GS) and healthy volunteers. METHODS: We enrolled consecutive patients with GBC (cases), GS (disease controls), and healthy volunteers (healthy controls). Serum CA 242, CEA, and CA 19-9 levels were measured using ELISA. Receiver operator curve was plotted for all the three markers. RESULTS: We studied 117 patients with GBC, 58 with GS, and 10 healthy volunteers. Among patients with GBC, 81 (69%) also had GB calculi. Patients with GBC more often had elevated CA 242 levels (64%) compared to those with GS (17%; p < 0.001) and healthy controls (0%; p < 0.001). The median levels of CA 242 was higher in the GBC group (59 [199] U/ml) compared to the GS group (10 [13] U/ml; p < 0.001) and the control group (3 [14.5] U/ml; p < 0.001). The sensitivity, specificity, positive predictive value (PPV), and negative predictive values of CA 242 for diagnosis of GBC were 64%, 83%, 88%, and 53%, respectively. At a cutoff of 45 U/ml, the specificity and PPV increased to 100%. CA 242 had higher AOC (0.759) compared to CEA (0.528) and CA 19-9 (0.430). CONCLUSIONS: CA 242 is a promising tumor marker for GBC and performs better than CEA and CA 19-9.


Asunto(s)
Antígenos de Carbohidratos Asociados a Tumores/sangre , Biomarcadores de Tumor/sangre , Neoplasias de la Vesícula Biliar/sangre , Área Bajo la Curva , Antígeno CA-19-9/sangre , Antígeno Carcinoembrionario/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Sensibilidad y Especificidad
19.
Mol Inform ; 30(4): 329-44, 2011 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-27466950

RESUMEN

Protein kinase C (PKC) has been the center of many cell signaling pathways. PKC isoforms, specifically PKC-ß II is linked to both diabetic complications as well as in promotion of angiogenesis and regulation of cancers. PKC-ß II activates the PKB/Akt pathway. Enzastaurin, a selective PKC-ß II inhibitor has been found to inhibit PKB/Akt by suppressing the regulation of various cancerous pathways. In the present work, we carried out an in depth study on the binding mode of inhibitors of PKC-ß II, enzastaurin and ruboxistaurin with the active site residues of PKB and PKC-ß II. A ligand based approach has been further used to determine the pharmacophoric features and spatial arrangement of molecules, having common properties necessary for appropriate binding to the active site of both targets. Virtual screening of the respective pharmacophores of both proteins led to identification of hits which may be useful for treatment of diabetic complications and cancer. The study has highlighted important features that may be considered in the future for designing novel inhibitors.

20.
Mol Inform ; 30(1): 45-62, 2011 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-27467877

RESUMEN

Diabetes causes contractile myocardial dysfunction through accelerated atherosclerosis and hypertension, termed Diabetic Cardiomyopathy. Experimental results reveals liaison between cardiovascular disease and diabetic complications. Protein kinase C (PKC), a heterogeneous family of phospholipid dependent kinases was found to be specifically involved in diabetic complications, of which PKC-ß II isoform played a significant role in induction of this fatal disease. Members of PKC family share high degree of similarity in both structure and functions, which has given rise to specificity related issues. In the present study, we have designed peptides and peptidomimetics based on RACK 1 (Receptor for Activated C Kinases) region, as this protein increases the substrate phosphorylation and stabilizes the activated form of PKC-ß II. RACK 1 being specific for PKC-ß II could resolve the specificity issue and also peptides and peptidomimetics, being conformationally restrained structures offers potential advantages of being used as drug molecules over organic molecules. This study has provided useful insights that may contribute to the development of molecules which may be useful in the treatment of diabetic complications.

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