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1.
J Pharm Bioallied Sci ; 15(Suppl 1): S299-S302, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37654384

RESUMEN

Introduction: Transversus abdominis plane (TAP) block is a technique of regional anesthesia, introduced by Rafi in 2001. Various additives have been added to prolong the duration of effect of TAP block. We conducted this study to see if addition of clonidine to bupivacaine significantly increases the duration of effect of TAP block. Materials and Methods: This randomized, parallel group, placebo controlled double blind clinical trial was conducted on 100 healthy participants (ASAII) undergoing LSCS under Spinal anesthesia (SA) from Jan 2021 to July 2021 after consent of Institutional Ethics Committee. Women with contraindications to spinal anesthesia, allergy to any of the drugs or not-suitable for cesarean under SA were excluded. After written informed consent, eligible participants were randomly allocated into two groups using computer generated random number tables using serially numbered opaque sealed envelopes. 48 out of 50 participants in group A (Bupivacaine) were given TAP block with 20 ml of 0.25% bupivacaine bilaterally. 2 women were excluded because of conversion to General Anesthesia. Similarly, 47 out of 50 participants in Group B (Bupivacaine + Clonidine) were given TAP block with 20 ml of 0.25% bupivacaine plus 1.0 mcg/kg clonidine bilaterally after completion of surgery using 18 G Tuohy needle. Separate person used to fill the drugs for block. Participants were assessed for duration of analgesic effect of TAP block measured as the time to request for additional analgesia. Additional analgesic requirement was noted. Participants were assessed for side effects of clonidine like hypotension, bradycardia, sedation and dryness of mouth. Overall patient satisfaction was also noted. Data was analysed using Graphpad Prism 9, using Student's t-test for primary outcome and Mann-Whitney U test for secondary outcomes. Results: The mean 'duration of analgesic effect with TAP block' was 6.34 (SD1.26) hrs for 'Bupivacaine' group and 10.56 (SD2.12) hrs for 'Bupivacaine + Clonidine' group. None of the patients developed hypotension or bradycardia. 25% participants in Bupivacaine only group and 40.42% in Bupivacaine + Clonidine group were sedated (P < 0.05). 20.8% in 'Bupivacaine' group and 51.06% in 'Bupivacaine + Clonidine' group had dryness of mouth (P < 0.001). Patient satisfaction was equal in both the groups. Conclusion: Addition of clonidine to bupivacaine in the dose of 1 mcg/kg significantly increases the duration of analgesic effect of TAP block, decreases analgesic usage without significant increase in side effects.

2.
J Pharm Bioallied Sci ; 15(Suppl 2): S920-S922, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37693962

RESUMEN

Background: To evaluate the prospects for dental implants in people with diabetes. Materials and Methods: Thirty patients in all were enrolled. The age range was from 40 to 60. Out of 30, 8 men and 22 women were present. HbA1c values were calculated. HbA1c levels and the ratio of problems to implant numbers were shown to be correlated. Data were gathered. Software called SPSS was used to analyses the results. Results: Thirty patients in all were enrolled. In follow-up cases, the stratification levels of HbA1c were investigated. The implant failure rate in 8.0-8.9 was 90.91%, with 2 implants failing. The survival rate in 11.0-11.9 was 75%. Others had a 100% success rate. Conclusion: Patients with diabetes have higher implant survival rates and fewer problems.

3.
J Gen Intern Med ; 38(14): 3134-3143, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37620721

RESUMEN

BACKGROUND: Clinical guidelines recommend that older patients (65+) with mild cognitive impairment (MCI) and early-stage dementia receive similar guideline-concordant care after cardiovascular disease (CVD) events as those with normal cognition (NC). However, older patients with MCI and dementia receive less care for CVD and other conditions than those with NC. Whether physician recommendations for guideline-concordant treatments after two common CVD events, acute myocardial infarction (AMI) and acute ischemic stroke (stroke), differ between older patients with NC, MCI, and early-stage dementia is unknown. OBJECTIVE: To test the influence of patient cognitive status (NC, MCI, early-stage dementia) on physicians' recommendations for guideline-concordant treatments for AMI and stroke. DESIGN: We conducted two parallel, randomized survey studies for AMI and stroke in the US using clinical vignettes where the hypothetical patient's cognitive status was randomized between physicians. PARTICIPANTS: The study included cardiologists, neurologists, and generalists who care for most patients hospitalized for AMI and stroke. MAIN MEASURES: The primary outcome was a composite quality score representing the number of five guideline-concordant treatments physicians recommended for a hypothetical patient after AMI or stroke. KEY RESULTS: 1,031 physicians completed the study (58.5% response rate). Of 1,031 respondents, 980 physicians had complete information. After adjusting for physician factors, physicians recommended similar treatments after AMI and stroke in hypothetical patients with pre-existing MCI (adjusted ratio of expected composite quality score, 0.98 [95% CI, 0.94, 1.02]; P = 0.36) as hypothetical patients with NC. Physicians recommended fewer treatments to hypothetical patients with pre-existing early-stage dementia than to hypothetical patients with NC (adjusted ratio of expected composite quality score, 0.90 [0.86, 0.94]; P < 0.001). CONCLUSION: In these randomized survey studies, physicians recommended fewer guideline-concordant AMI and stroke treatments to hypothetical patients with early-stage dementia than those with NC. We did not find evidence that physicians recommend fewer treatments to hypothetical patients with MCI than those with NC.


Asunto(s)
Enfermedades Cardiovasculares , Demencia , Accidente Cerebrovascular Isquémico , Infarto del Miocardio , Médicos , Accidente Cerebrovascular , Humanos , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/terapia , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/terapia , Cognición , Encuestas y Cuestionarios , Demencia/epidemiología , Demencia/terapia
4.
Cureus ; 15(5): e38919, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37309345

RESUMEN

Objective This cross-sectional case-control study was conducted with the aim to analyze spirometric lung functions in type 2 diabetes mellitus (T2DM) patients and to correlate the spirometric dysfunction with (a) duration of diabetes, b) metabolic control of diabetes, and c) microvascular complications of diabetes. Methods Pulmonary function tests (PFTs) were performed in 50 T2DM patients and 50 normal healthy controls aged <80 years by using an electronic spirometer. The PFTs recorded were as follows: forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1%, forced expiratory flow 25 (FEF25), forced expiratory flow 25-75 (FEF25-75), and peak expiratory flow rate (PEFR). The glycated hemoglobin (HbA1c) of all the patients was measured by affinity chromatography using the NycoCard HbA1C kit. The assessment of diabetic microvascular complications was performed as follows: peripheral neuropathy was done using Michigan Neuropathy Screening Instrument (MNSI), diabetic retinopathy using fundus examination, and diabetic nephropathy using solid phase/sandwich-format/immunometric assay using NycoCard U-albumin kit. PFTs of diabetic patients and controls were compared by applying an independent sample t-test. The correlation between FVC and FEV1, and HbA1c and duration of illness in diabetic patients was analyzed by applying the Pearson coefficient. Results  The cases had low FVC (103.82 ±24.43 vs. 116.08 ±13.66), FEV1 (101.36 ±24.23 vs. 110.26 ±14.39), FEV1% (97.56 ±8.64 vs. 103.84 ±5.06), PEFR (101.52 ±27.18 vs. 116.96 ±14.96), and FEF 25-75 (73.56 ±29.19 vs. 98.40 ±14.45) compared to controls, and the difference was statistically significant. A significant negative correlation was found between spirometry parameters and duration of illness as well as HbA1c. Spirometric lung dysfunction also negatively correlated with microvascular complications of diabetes. Among various microvascular complications, retinopathy correlated best with various spirometric parameters. Conclusion Based on our findings, T2DM patients had a significant decrease in their spirometric indices. The pattern of spirometric dysfunction was suggestive of "mixed ventilatory dysfunction". The study results highlight the need to include PFTs in the periodic check-up as part of the comprehensive management of diabetic patients. Hence, pulmonary function should be included in the periodic comprehensive diabetic check for the holistic management of these patients.

5.
Cureus ; 15(3): e36530, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37090397

RESUMEN

Background In this cohort study, the association between periodontal disease (PD) and recurrent vascular events was determined among the subjects with ischemic stroke/transient ischemic attack (TIA), and the extent and severity of periodontal disease were estimated among these subjects. Methods This prospective, longitudinal, hospital-based cohort study included 153 individuals who had a stroke or TIA. They were divided into two groups: high periodontal disease (HPD) (N=55, mean age: 59.40±12.21) and low periodontal disease (LPD) (N=98, mean age: 53.03±12.82). Clinical attachment loss (CAL) and probing pocket depth (PPD) were used to measure the severity of the periodontal disease. TOAST criteria were used to determine the ischemic stroke etiology, and the NIH Stroke Scale (NIHSS) was used to determine the ischemic stroke severity. A follow-up survey found that vascular incidents recurred. Results HPD individuals exhibited a higher median NIHSS (eight) than LPD patients (seven) in a subset of stroke population (N=23). Thirty-eight cardiovascular events occurred in the first three months after enrollment, including 23 strokes and seven TIAs, and five myocardial infarctions(MIs). There were three deaths from vascular causes. There was a non-significant association between PD and composite vascular events (HR 1.06, 95% CI, 1.03 to 1.09, p=0.71). Compound vascular events were not related to severe HPD (HR 1.31, 95 % CI 0.54 to 3.16, p=0.07). Conclusion In stroke/TIA patients, there is no link between high periodontal disease and recurrent vascular episodes. The proportions of stroke subtypes were not substantially different between HPD and LPD.

6.
J Pharm Bioallied Sci ; 14(Suppl 1): S209-S213, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36110769

RESUMEN

Introduction: Almost every cesarean delivery is done under spinal anesthesia because of ease of doing, rapid onset, avoids maternal and fetal risk of general anesthesia, promotes early recovery. Major complication especially in young women undergoing LSCS under spinal anesthesia is post dural puncture headache (PDPH) which is caused by cerebrospinal fluid leakage. There is wide variation in reported incidence of PDPH (0.3% to 40 %) after spinal anesthesia being affected by various procedure and non procedure related risk factors like age, gender, needle size and type, numbers of spinal attempts and previous history of PDPH. Methods: Prospective cohort study was conducted in 335 patients posted for caesarean section under spinal anesthesia from January 2019 to September 2019 in medical College situated in rural India. Spinal anesthesia was given by 26 G Quincke spinal needle. All patients were evaluated for incidence and severity of PDPH from post operative day 1 to day 5. Result: Incidence of PDPH was 11.4% in this study. Majority of patients (62.5%) were having mild pain. All patients reported PDPH with 72 hours. Conclusion: Body mass index (BMI), h/o PDPH, multiple attempts for successful spinal anesthesia did not have any significant association with PDPH in our study.

7.
J Int Soc Prev Community Dent ; 12(3): 365-375, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35966910

RESUMEN

Introduction: Visually enhanced lesion scope (Velscope) that identifies reduction in tissue fluorescence in dysplasia can prove to be effective in screening for potentially malignant lesions. The objective of the present study was to evaluate the effectiveness of device that utilizes the principles of tissue autofluorescence (Velscope) in the detection of dysplastic and/or neoplastic changes in oral mucosal lesions using biopsy and histopathology as "gold standard." Materials and Methods: Out of nine hundred fifty patients with suspicious oral mucosal lesions, 250 patients were subjected to conventional oral examination followed by Velscope examination. The autofluorescence characteristics of 250 patients were compared with the results of histopathology. Biopsies were obtained from all suspicious areas identified on examination. The sensitivity, specificity, positive and negative predictive values were calculated for Velscope examination. Results: The Velscope examination showed sensitivity and specificity values of 75.00% (95% CI: 69.63%-80.37%) and 61.39% (95% CI: 55.35%-67.42%) respectively while the positive and negative predictive values were 31.58% (95% CI: 25.82%-37.34%) and 91.18% (95% CI: 87.66%-94.69%) respectively. Conclusion: The definite diagnosis of the presence of dysplastic tissue changes in the oral lesions cannot be made alone with the Velscopic examination. The high number of false-positive results limits its efficiency as an adjunct despite its reasonable sensitivity. However, It can serve to alleviate patient anxiety regarding suspicious mucosal lesions in a general practice setting due to high negative predictive value. Also, a combined approach of Velscope examination and conventional oral examination may prove to be an effective diagnostic tool for early detection of malignant oral mucosal lesions.

8.
Am J Prev Med ; 60(5): 716-725, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33775514

RESUMEN

CONTEXT: E-cigarette use is increasing among adolescents, particularly in high-income countries. This review examines the health perceptions of E-cigarettes among adolescents (aged 12-17 years) residing in the U.S., United Kingdom, Canada, Australia, and New Zealand and their sources of E-cigarette information. EVIDENCE ACQUISITION: Peer-reviewed literature published in January 2009-April 2019 in MEDLINE, Embase, and ProQuest were systematically reviewed using identified keywords. The search identified 654 references. Studies (n=99) that met the inclusion criteria were subjected to full-text screening. A total of 27 articles were subjected to quality appraisal using the Joanna Briggs Institute's critical appraisal checklists. EVIDENCE SYNTHESIS: A total of 7 qualitative and 18 quantitative studies were included in the review, and the study characteristics, results, and limitations were extracted. A total of 4 main themes emerged from the study findings: (1) perceived relative harm of E-cigarettes versus that of cigarettes, (2) perceived health effects of E-cigarettes, (3) perceived benefits and safety of E-cigarettes, and (4) sources of E-cigarette information and exposure. Most adolescents perceived E-cigarettes to be less harmful than cigarettes; however, often, their health perceptions of E-cigarettes were conflicting. Sources of exposure to E-cigarette information included friends, family, retail point of sale, TV and online advertising, national agencies, healthcare providers, and from direct experience. CONCLUSIONS: Findings indicate that adolescents, particularly E-cigarette users, have more favorable perceptions of E-cigarettes than of cigarettes; however, these perceptions are conflicting. Advertising, marketing, and peer and family networks appear to influence adolescents' perceptions. More research is required, particularly in Australia and New Zealand, to better understand adolescents' health perceptions of E-cigarettes and where they source information from so that misperceptions can be addressed through appropriate channels with suitable messaging.


Asunto(s)
Sistemas Electrónicos de Liberación de Nicotina , Adolescente , Australia , Canadá , Humanos , Nueva Zelanda , Percepción , Reino Unido
9.
J Stroke Cerebrovasc Dis ; 24(2): 337-47, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25444031

RESUMEN

BACKGROUND: Although chronic risk factors for stroke are reasonably well understood, the acute precipitants, or triggers, of stroke relatively remain understudied. Identification of particular time periods during which stroke risk is elevated could prove a valuable strategy to reduce stroke incidence through the introduction of appropriate prevention strategies during a period of vulnerability. The aim of this study was to determine the prevalence of trigger factors in acute stroke patients and to investigate the association of the presence of trigger factors with initial stroke severity at presentation (National Institutes of Health Stroke Scale (NIHSS) score in ischemic stroke patients and volume of hematoma in hemorrhagic stroke patients). METHODS: This was a hospital-based observational cross-sectional study. All consecutive patients of recent stroke (reporting within 1 week of stroke onset) were included in the study. This study examined the prevalence of 11 predefined triggers (including both well-established and potential triggers) in predefined hazard periods. RESULTS: In total, 290 patients participated in the study. Presence of any trigger factor out of 11 trigger factors studied was seen in 128 (44.2%) of 290 patients, 104 (46.4%) of 224 ischemic stroke patients and 24 (36.4%) of 66 hemorrhagic stroke patients. Psychological stress was present in 51 (17.6%) patients, among psychological stress: stressful life event in 34 (11.7%), negative affect in 17 (5.9%), acute alcohol abuse in 31 (10.7%), clinical infections in 24 (8.3%), and anger and coffee intake in 12 (4.1%) each. Sexual activity, trauma, and surgery were present in 5 (1.7%), 4 (1.4%), and 5 (1.7%) patients, respectively. None of the patients reported exposure to recreational drug abuse, startling event, and unusual vigorous physical exertion in hazard periods. Two or more trigger factors were present in 16 (5.5%) patients. Clinical variables independently associated with the presence of trigger factors in acute stroke after multivariate analysis were younger age (<60 years) and stroke severity at initial presentation (ie, higher NIHSS score and higher hematoma volume). CONCLUSIONS: Trigger factors were present in 44.2% of acute stroke patients. Psychological stress (17.6%), acute alcohol abuse (10.7%), and clinical infections (8.3%) were the most common triggers. Younger age (<60 years) and stroke severity at initial presentation were independently associated with the presence of trigger factors in acute stroke patients. However, these associations need to be further explored in community-based studies.


Asunto(s)
Alcoholismo/complicaciones , Isquemia Encefálica/etiología , Estrés Psicológico/complicaciones , Accidente Cerebrovascular/etiología , Adulto , Anciano , Anciano de 80 o más Años , Alcoholismo/epidemiología , Isquemia Encefálica/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Estrés Psicológico/epidemiología , Accidente Cerebrovascular/epidemiología , Factores de Tiempo
10.
J Indian Soc Periodontol ; 18(6): 762-6, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25624634

RESUMEN

BACKGROUND: Oral diseases such as gingival diseases and dental caries affect about 80% of the school students worldwide. The study was taken up with the aim to evaluate the oral health status and treatment need in the School going children of Nagrota Bagwan Block of Kangra District, Himachal Pradesh. MATERIALS AND METHODS: A total number of 3069 school children in the age group of 5-12 years studying in 96 government primary schools of study area were surveyed to find out the Oral Hygiene Index simplified (OHI-S) scores, community periodontal index (CPI) scores, dental caries and treatment need using dentition status and treatment need index (WHO diagnostic criteria, 1997). RESULTS: The mean OHI-S was 2.7 ± 2.81and 2.8 ± 2.99 in 5-8 and 9-12 years age group, respectively. The gingival bleeding was observed in 76.8% and 75.9%, calculus in 10.2% and 18.3% in 5-8 and 9-12 years age group, respectively. The overall caries prevalence of subjects was 58.4% with high caries prevalence in females as compared to males and in 9-12 years age group as compared to 5-8 years age group. The mean dmft/DMFT was 2.05 ± 4.13 and 2.56 ± 4.20 in 5-8 years and 9-12 years age group, respectively. Treatment need observed was 62.3% and 75.3% in 5-8 and 9-12 years age group, respectively. CONCLUSION: The study demonstrated that school children in Nagrota Bagwan, Kangra district suffer from high prevalence of dental caries and have high treatment need as well as poor oral hygiene and gingival health status.

11.
J Indian Soc Periodontol ; 17(3): 373-7, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-24049340

RESUMEN

Papillon-Lefèvre syndrome (PLS) is a very rare syndrome of autosomal recessive inheritance characterized by palmar-plantar hyperkeratosis and early onset periodontitis, leading to premature loss of both primary and permanent dentitions. Various etiopathogenic factors are associated with the syndrome, but a recent report has suggested that the condition is linked to x mutations of the cathepsin C gene. The purpose of this report is to describe two cases of PLS in the same family who presented to the Department of Dentistry of Dr. R. P. Government Medical College at Tanda, Kangra (Himachal Pradesh) with a chief complaint of mobility and rapid loss of teeth. Hyperkeratosis of palms and soles was present. On intraoral examination, there was severe gingival inflammation, abscess formation, and deep periodontal pockets with mobility of teeth. Histopathological examination of the specimen taken from the thickened skin was reported to be consistent with PLS. The dental treatment comprised oral prophylaxis, scaling and root planning, antibiotic therapy, instructions on oral hygiene, restorations, extraction of hopelessly affected teeth, and prosthetic rehabilitation.

13.
J Indian Soc Periodontol ; 13(3): 145-9, 2009 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20379412

RESUMEN

BACKGROUND AND OBJECTIVES: Circulating C-reactive protein (CRP) levels are a marker of systemic inflammation and are associated with periodontal disease, a chronic bacterial infection associated with elevation of proinflammatory cytokines and prostaglandins. CRP has been associated with adverse pregnancy outcomes, including preterm delivery, preeclampsia, and intrauterine growth restriction. Furthermore, periodontal disease has been associated with increased risk of preterm low birth weight, low birth weight, and preterm birth. The present study was conducted to assess plasma CRP levels in pregnant women with and without periodontal disease; to evaluate the effect of periodontal therapy on the incidence of preterm delivery; and to compare the incidence of preterm delivery in pregnant women with and without periodontal disease. MATERIALS AND METHODS: A total of 90 pregnant women aged between 18-35 years with gestational age between 12-28 weeks were recruited and divided into three equal groups (control group, study group, treatment group) of 30 each. Blood samples were taken for estimation of C-reactive protein levels from all groups at 12-20 weeks of gestation, determined using ultrasensitive turbidimetric immunoassay (QUANTIA-CRP US). The treatment group comprised plaque control, scaling, and root planning and daily rinsing with 0.2% chlorhexidine mouth before 28 weeks of gestation. RESULTS: The mean value of C-reactive protein levels in subjects with periodontal disease was higher compared to control group i.e., 1.20 +/- 0.247 mg/dl and 1.22 +/- 0.250 mg/dl, respectively, compared to 0.713 +/- 0.139 mg/ dl (P = 0.001). The mean value of CRP levels before treatment was greater than the mean value after treatment i.e., 1.22 +/- 0.25 compared to 0.84 +/- 0.189 (P < 0.001). The incidence of preterm delivery (< 37 weeks) was 31.7% in the periodontal disease group (study group) compared to 8.3% in the control group (P = 0.001). The incidence of preterm delivery in the treatment group was 15.0% compared to 31.7% in the nontreatment group (study group). CONCLUSION: The findings from the study suggest that periodontal disease in pregnant women is associated with increased C- reactive protein levels in early pregnancy, incidence of preterm delivery is higher in pregnant women with periodontal disease compared to healthy controls, periodontal therapy during pregnancy reduces plasma CRP levels and there is decrease in incidence of preterm delivery after periodontal therapy.

14.
J Cell Biochem ; 102(1): 1-12, 2007 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-17668438

RESUMEN

Osteoclastic bone resorption is a central mechanism in skeletal development, remodeling and pathology. RANKL is a mandatory factor controlling osteoclastogenesis; however, the underlying signaling pathways are only partially characterized. Using a screening array for the investigation of differential transcription factor activation, we identified activation of the Brn3 transcription factor family as a downstream event of RANKL signaling during terminal osteoclastogenesis. RANKL stimulation induces expression of Brn3a and b and maximal transcriptional activity of Brn3 family members concurrent with osteoclastic giant cell formation. Immunohistochemical analysis revealed both nuclear and cytoplasmic localization of Brn3a and b in mature osteoclasts. Functional inhibition of Brn3 transcription factors resulted in inhibition of pre-osteoclast fusion and reduction in bone resorbing activity of mature osteoclasts. Furthermore, we identified synaptotagmin-1, a regulator of membrane and vesicular fusion, as downstream target of Brn3 with a role in osteoclast function. We conclude that Brn-3 represents a novel molecular differentiation factor that controls osteoclast maturation and function, suggesting an important role in bone metabolism.


Asunto(s)
Proteínas de Homeodominio/fisiología , Osteoclastos/fisiología , Factor de Transcripción Brn-3A/fisiología , Factor de Transcripción Brn-3B/fisiología , Animales , Secuencia de Bases , Resorción Ósea , Diferenciación Celular , Células Cultivadas , Secuencia de Consenso , Proteínas de Homeodominio/antagonistas & inhibidores , Proteínas de Homeodominio/metabolismo , Ratones , Ratones Endogámicos BALB C , Oligonucleótidos/química , Osteoclastos/citología , Osteoclastos/metabolismo , Sinaptotagmina I/fisiología , Factor de Transcripción Brn-3A/antagonistas & inhibidores , Factor de Transcripción Brn-3A/metabolismo , Factor de Transcripción Brn-3B/antagonistas & inhibidores , Factor de Transcripción Brn-3B/metabolismo , Activación Transcripcional
15.
Am J Physiol Gastrointest Liver Physiol ; 289(4): G686-95, 2005 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-15976386

RESUMEN

Pancreatic acini secrete digestive enzymes in response to a variety of secretagogues including CCK and agonists acting via proteinase-activated receptor-2 (PAR2). We employed the CCK analog caerulein and the PAR2-activating peptide SLIGRL-NH(2) to compare and contrast Ca(2+) changes and amylase secretion triggered by CCK receptor and PAR2 stimulation. We found that secretion stimulated by both agonists is dependent on a rise in cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) and that this rise in [Ca(2+)](i) reflects both the release of Ca(2+) from intracellular stores and accelerated Ca(2+) influx. Both agonists, at low concentrations, elicit oscillatory [Ca(2+)](i) changes, and both trigger a peak plateau [Ca(2+)](i) change at high concentrations. Although the two agonists elicit similar rates of amylase secretion, the rise in [Ca(2+)](i) elicited by caerulein is greater than that elicited by SLIGRL-NH(2). In Ca(2+)-free medium, the rise in [Ca(2+)](i) elicited by SLIGRL-NH(2) is prevented by the prior addition of a supramaximally stimulating concentration of caerulein, but the reverse is not true; the rise elicited by caerulein is neither prevented nor reduced by prior addition of SLIGRL-NH(2). Both the oscillatory and the peak plateau [Ca(2+)](i) changes that follow PAR2 stimulation are prevented by the phospholipase C (PLC) inhibitor U73122, but U73122 prevents only the oscillatory [Ca(2+)](i) changes triggered by caerulein. We conclude that 1) both PAR2 and CCK stimulation trigger amylase secretion that is dependent on a rise in [Ca(2+)](i) and that [Ca(2+)](i) rise reflects release of calcium from intracellular stores as well as accelerated influx of extracellular calcium; 2) PLC mediates both the oscillatory and the peak plateau rise in [Ca(2+)](i) elicited by PAR2 but only the oscillatory rise in [Ca(2+)](i) elicited by CCK stimulation; and 3) the rate of amylase secretion elicited by agonists acting via different types of receptors may not correlate with the magnitude of the [Ca(2+)](i) rise triggered by those different types of secretagogue.


Asunto(s)
Amilasas/metabolismo , Calcio/fisiología , Colecistoquinina/fisiología , Páncreas/metabolismo , Receptor PAR-2/fisiología , Animales , Ceruletida/farmacología , Inhibidores Enzimáticos/farmacología , Estrenos/farmacología , Técnicas In Vitro , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Oligopéptidos/farmacología , Páncreas/citología , Páncreas/efectos de los fármacos , Inhibidores de Fosfodiesterasa/farmacología , Pirrolidinonas/farmacología , Receptores de Colecistoquinina/efectos de los fármacos , Fosfolipasas de Tipo C/antagonistas & inhibidores
16.
Am J Physiol Gastrointest Liver Physiol ; 288(2): G388-95, 2005 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-15458925

RESUMEN

Protease-activated receptor-2 (PAR-2) is a widely expressed tethered ligand receptor that can be activated by trypsin and other trypsin-like serine proteases. In the exocrine pancreas, PAR-2 activation modulates acinar cell secretion of digestive enzymes and duct cell ion channel function. During acute pancreatitis, digestive enzyme zymogens, including trypsinogen, are activated within the pancreas. We hypothesized that trypsin, acting via PAR-2, might regulate the severity of that disease, and to test this hypothesis, we examined the effect of either genetically deleting or pharmacologically activating PAR-2 on the severity of secretagogue-induced experimental pancreatitis. We found that experimental acute pancreatitis is more severe in PAR-2(-/-) than in wild-type mice and that in vivo activation of PAR-2, achieved by parenteral administration of the PAR-2-activating peptide SLIGRL-NH2, reduces the severity of pancreatitis. In the pancreas during the early stages of pancreatitis, the MAPK ERK1/2 is activated and translocated to the nucleus, but nuclear translocation is reduced by activation of PAR-2. Our findings indicate that PAR-2 exerts a protective effect on pancreatitis and that activation of PAR-2 ameliorates pancreatitis, possibly by inhibiting ERK1/2 translocation to the nucleus. Our observations suggest that PAR-2 activation may be of therapeutic value in the treatment and/or prevention of severe clinical pancreatitis, and they lead us to speculate that, from a teleological standpoint, PAR-2 may have evolved in the pancreas as a protective mechanism designed to dampen the injurious effects of intrapancreatic trypsinogen activation.


Asunto(s)
Pancreatitis/fisiopatología , Receptor PAR-2/fisiología , Animales , Ceruletida , Activación Enzimática , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Oligopéptidos/farmacología , Pancreatitis/inducido químicamente , Pancreatitis/metabolismo , Péptidos/farmacología , Receptor PAR-2/genética , Receptor PAR-2/metabolismo
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