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1.
Braz J Biol ; 83: e246776, 2023.
Article in English | MEDLINE | ID: mdl-36629624

ABSTRACT

The study was aimed to identify different environmental factors (selected organochlorine pesticides) affecting the river water of Satluj. River Sutlej is about 1400 kilometers long and its water is extensively used for irrigation in Punjab, located both in India and Pakistan, which was also a reason of dispute between both countries for its water share. The study area was divided into four zones, Sulemanki Zone, Islam Zone, Mailsi Syphone Zone and Panjnad Zone. Liquid Liquid Extraction (LLE) technique was used for the collected water samples followed by high performance liquid chromatography (HPLC) UV-Visible detector The current finding revealed that aldrin was not detected during summer period in water samples of SZ-1 (Sulemanki Barrage), SZ-2 and SZ-3 (Maisli Siphon) of the study area. Lindane and DDE were found more in the samples of sediments from the study area at SZ-4 ranging from 2.238-8.226 ppb and 4.234-6.876 ppb, respectively. Heaptachlor (in sediments) was found to be0.032-234 ppb only at SZ-4.Endosulfan concentrations in water (winter) at SZ-3 was 0.06 ppb and at SZ-4,it was 0.05 ppb; dieldrin in water (winter) at SZ-4 was 0.0314 ppb and heptachlor was detected at SZ-1 (0.0315 ppb) and SZ-2 (0.0310 ppb) in water during winter season, were reaching to the Maximum Concentrations Limits (MCL), while all other residues investigated were found below the MCLin all the compartments of the study area set by various agencies like WHO/FAO- Codex Alimenterious. Present findings revealed that although the organochlorine pesticides are banned for agricultural use in many countries, including Pakistan, their presence in various samples might be due to illegal use of these pesticides in the study area and its neighboring regions. The overall study area comprises of mainly urban, suburban and agricultural land being the largest cotton growing area of the country. There is a need to take serious steps to minimize water pollution caused by pesticides to achieve a healthy lifestyle.


Subject(s)
Hydrocarbons, Chlorinated , Pesticides , Water Pollutants, Chemical , Rivers/chemistry , Pakistan , Water , Water Pollutants, Chemical/analysis , Pesticides/analysis , Hydrocarbons, Chlorinated/analysis , Environmental Monitoring
2.
Braz J Biol ; 83: e243905, 2022.
Article in English | MEDLINE | ID: mdl-36383902

ABSTRACT

In the developed countries, the use of OCPs (organochlorine pesticides) has been banned. However, in South Asia several of them are still in use. In Pakistan and India a constant addition of OCPs into the atmosphere has been indicated by various researchers. In this study levels of selected organochlorine pesticide residues were assessed in sediment and biota collected from four (4) water reservoirs (3 Barrages & 1 Siphon) on the River Satluj Pakistan, along 231 miles (372 km) of River stretch which was further divided into 12 sampling sites. It was aimed to find out the levels of organochlorine pesticide (OCPs) residues in sediments and from selected fish species (Labeo rohita, Wallagu attu, Cyprinus carpio) of the River Satluj Pakistan. The Organochlorine residues (seven pesticides) present in samples of sediments and biota were investigated through multi residue method, using Gas Chromatograph (GC-ECD).In the current study, the concentration of DDT, was investigated in Wallago attu (0.786-3.987 ppb), Labeo rohita (0.779-4.355 ppb) and Cyprinus carpio (1.234-5.654 ppb). DDE was also found in Cyprinus carpio (1.244-6.322 ppb), Wallag attu (0.877-4.221 ppb) and Labeo rohita (2.112-5.897 ppb). Aldrin was not observed in Labeo rohita and Wallago attu. Currently, lindane and DDE was found predominately high in the sediments of study area at SZ-4 (Panjnad Barrage) ranging (2.238-8.226 ppb) and (4.234-6.876 ppb), respectively. Heaptachlor was found only at SZ-4 (Panjnad Barrage) from the sediments with concentration ranging (0.032-234 ppb). In short all other residues investigated were found below the MCL (maximum concentration level) in all the compartments of the study area set by various agencies like WHO/FAO- Codex Alimenterious.


Subject(s)
Carps , Hydrocarbons, Chlorinated , Pesticides , Water Pollutants, Chemical , Animals , Rivers/chemistry , Dichlorodiphenyl Dichloroethylene/analysis , Pakistan , Geologic Sediments/chemistry , Environmental Monitoring/methods , Water Pollutants, Chemical/analysis , Hydrocarbons, Chlorinated/analysis , Pesticides/analysis , Biota
3.
Curr Diabetes Rev ; 18(9): e301221199656, 2022.
Article in English | MEDLINE | ID: mdl-34967298

ABSTRACT

Despite substantial investment in research and treatment options, diabetes mellitus remains a pressing public health concern with potential epidemic proportions globally. There are reports that by the end of 2040, 642 million people will be suffering from diabetes. Also, according to an estimation, 1.6 million deaths were caused directly by diabetes in 2016. Diabetes is a metabolic disorder characterized by impaired glucose regulation in the body due to the destruction of pancreatic ß-cells or insulin resistance. Genetic propensity, unhealthy and imbalanced diet, obesity and increasing urbanization are the common risk factors for diabetes. Besides this, it has been reported that environmental pollutants like organic pesticides, heavy metals, and air pollutants act as strong predisposing factors for diabetes owing to their highly bio-accumulative nature. These pollutants disturb glucose homeostasis either by up-regulating or down-regulating the expression of diabetic marker genes like insulin (INS) and glucokinase (GCK). Unfortunately, the molecular mechanism of the role of pollutants in causing diabetes is not very clear. This mechanistic review provides evidence of different environmental determinants, including persistent organic pollutants (POPs), air pollutants, toxic metals, etc., in inducing diabetes and proposes a framework for the possible mechanisms involved. It also illuminates the current status and future challenges, which will not only broaden our understanding but can also be a reasonable platform for further investigation.


Subject(s)
Air Pollutants , Diabetes Mellitus , Environmental Pollutants , Insulin Resistance , Diabetes Mellitus/epidemiology , Diabetes Mellitus/etiology , Environmental Pollutants/toxicity , Glucose , Humans , Insulin Resistance/physiology
4.
Drug Res (Stuttg) ; 66(3): 121-5, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26011814

ABSTRACT

The present study explores the fungal endophytes from selected high value medicinal plants to check their activities at in-vitro and in-vivo level. The in-vitro cytotoxicity of selected endophytes revealed potent growth inhibition against human cancer cell lines of leukemia (THP-1), lung (A549), prostate (PC-3), colon (Caco-2), neuroblastoma (IMR-32) and breast (MCF-7) at a concentration of 100 µg/ml. Among them the endophytic strains I. e., IIIM2, IIIM3, IIIM7 and IIIM8 showed most significant growth inhibition against colon (Caco-2), prostate (PC-3), lung (A549) and leukemia (THP-1) cancer cell lines. At the in-vivo level maximum (58.95%) tumor growth inhibition was documented with the extract of IIIM2 against Ehrlich Ascites Carcinoma mouse modal. All the potent fungal endophytic strains were characterized using ITS 4 and ITS 5 region sequencing and phylogenetic analysis was ascertained among them. This paper confirms the 2 elite endophytic fungal strains, IIIM2 and IIIM8, have the potential to act as a source of new anticancer compounds.


Subject(s)
Endophytes/chemistry , Fungi/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Plants, Medicinal/chemistry , A549 Cells , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Caco-2 Cells , Cell Line, Tumor , Humans , India , MCF-7 Cells , Mice , Phylogeny
5.
Z Gerontol Geriatr ; 48(4): 305-11, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25962363

ABSTRACT

Depression and cognitive disorders, including dementia and mild cognitive impairment, are common disorders in old age. Depression is frequent in dementia, causing distress, reducing the quality of life, exacerbating cognitive and functional impairment and increasing caregiver stress. Even mild levels of depression can significantly add to the functional impairment of dementia patients and the severity of psychopathological and neurological impairments increases with increasing severity of depression. Depressive symptoms may be both a risk factor for, as well as a prodrome of dementia. Major depressive syndrome of Alzheimer's disease may be among the most common mood disorders of older adults. Treating depression is therefore a key clinical priority to improve the quality of life both of people with dementia as well as their carergivers. Nonpharmacological approaches and watchful waiting should be attempted first in patients who present with mild to moderate depression and dementia. In cases of severe depression or depression not able to be managed through nonpharmacological means, antidepressant therapy should be considered.


Subject(s)
Alzheimer Disease/epidemiology , Depressive Disorder/epidemiology , Alzheimer Disease/diagnosis , Alzheimer Disease/psychology , Antidepressive Agents/therapeutic use , Caregivers/psychology , Comorbidity , Cost of Illness , Cross-Sectional Studies , Depressive Disorder/diagnosis , Depressive Disorder/drug therapy , Depressive Disorder/psychology , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/drug therapy , Depressive Disorder, Major/epidemiology , Depressive Disorder, Major/psychology , Humans , Quality of Life
6.
AJNR Am J Neuroradiol ; 36(6): 1076-80, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25907521

ABSTRACT

BACKGROUND AND PURPOSE: Acute statin therapy improves neurologic outcome and diminishes infarct growth in animal models of stroke. Clinical studies suggest that premorbid and early statin use is associated with improved outcome after major stroke. We studied the association between statin therapy and radiographic and clinical outcomes in patients with high-risk TIA and minor stroke. MATERIALS AND METHODS: Patients with high-risk TIA and minor stroke (NIHSS ≤3) were prospectively enrolled within 24 hours of symptom onset. Patients were followed clinically for 3 months, and a subset had a repeat MR imaging at 90 days. RESULTS: Of 418 patients, 23% were prescribed statins before their stroke. Statins were continued in 20% and initiated in 42%. Patients on prior statin therapy were older and more hypertensive, treated with aspirin, and more likely to have symptomatic carotid disease compared with those not on statin. Adjusting for these differences, prior statin treatment was not associated with DWI positivity (adjusted OR = 1.3; 95% CI, 0.77-2.1; P = .32) or smaller median baseline infarct volume, 1.1 mL (interquartile range = 4) versus 1 mL (interquartile range = 2.5; P = .56). Early or continued treatment with statins did not improve the risk of clinical deterioration (adjusted OR = 0.66; 95% CI, 0.27-1.6; P = .35) or poor functional outcome at 3 months (adjusted OR = 0.66; 95% CI, 0.35-1.24; P = .19). CONCLUSIONS: Prestroke or early-stroke statin therapy was not associated with a reduction in the number of DWI lesions, infarct volume, or improved clinical or functional outcome at 3 months. The effect of acute statin treatment in patients with ischemic stroke/TIA remains unclear and needs further investigation.


Subject(s)
Diffusion Magnetic Resonance Imaging , Early Medical Intervention , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Ischemic Attack, Transient/diagnosis , Stroke/diagnosis , Stroke/drug therapy , Tomography, X-Ray Computed , Aged , Aged, 80 and over , Disease Progression , Female , Humans , Male , Middle Aged , Neurologic Examination/drug effects , Recurrence , Treatment Outcome
7.
AJNR Am J Neuroradiol ; 35(4): 660-6, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24335541

ABSTRACT

BACKGROUND AND PURPOSE: More than half of patients with TIA/minor stroke have ischemic lesions on early DWI, which represent irreversibly damaged tissue. The presence and volume of DWI lesions predict early deterioration in this population. We aimed to study the rate and implications of DWI reversal in patients with TIA/minor stroke. MATERIALS AND METHODS: Patients with TIA/minor stroke were prospectively enrolled and imaged within 24 hours of onset. Patients were followed for 3 months with repeat MR imaging either at day 30 or 90. Baseline DWI/PWI and follow-up FLAIR final infarct volumes were measured. RESULTS: Of 418 patients included, 55.5% had DWI and 37% had PWI (time-to-peak of the impulse response ≥2 seconds' delay) lesions at baseline. The median time from symptom onset to baseline and follow-up imaging was 13.4 (interquartile range, 12.7) and 78.73 hours (interquartile range, 60.2), respectively. DWI reversal occurred in 5.7% of patients. The median DWI lesion volume was significantly smaller in those with reversal (0.26 mL, interquartile range = 0.58 mL) compared with those without (1.29 mL, interquartile range = 3.6 mL, P = .002); 72.7% of DWI reversal occurred in cortically based lesions. Concurrent tissue hypoperfusion (time-to-peak of the impulse response ≥2 seconds) was seen in 36.4% of those with DWI reversal versus 62.4% without (P = .08). DWI reversal occurred in 3.3% of patients with penumbral patterns (time-to-peak of the impulse response ≥6 seconds - DWI) > 0 and in 6.8% of those without penumbral patterns (P = .3). The severity of hypoperfusion, defined as greater prolongation of time-to-peak of the impulse response (≥2, ≥4, ≥6, ≥8 seconds), did not affect the likelihood of DWI reversal (linear trend, P = .147). No patient with DWI reversal had an mRS score of ≥2 at 90 days versus 18.2% of those without reversal (P = .02). CONCLUSIONS: DWI reversal is uncommon in patients with TIA/minor stroke and is more likely to occur in those with smaller baseline lesions. DWI reversal should not have a significant effect on the accuracy of penumbra definition.


Subject(s)
Cerebral Infarction/pathology , Diffusion Magnetic Resonance Imaging/methods , Ischemic Attack, Transient/pathology , Severity of Illness Index , Stroke/pathology , Aged , Aged, 80 and over , Brain/pathology , Diffusion Magnetic Resonance Imaging/standards , Female , Follow-Up Studies , Humans , Male , Predictive Value of Tests , Prospective Studies , Reproducibility of Results
9.
Ann R Coll Surg Engl ; 94(6): e186-8, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22943316

ABSTRACT

INTRODUCTION: The plastibell device is used successfully for religious and cultural circumcisions in the community. The aim of this article is to highlight the recognition and management of iatrogenic phimosis. METHODS: A retrospective study was performed of outcomes of plastibell circumcision in a community-based circumcision service provided by trained paediatric surgeons. The objective was to assess the complication of slipped plastibell rings and to ascertain the effectiveness of its management. RESULTS: A total of 5 patients with a slipped plastibell ring were indentified out of 560 plastibell circumcisions. Three patients presented with acquired phimosis. In two patients early diagnosis and management prevented any further complications and a second operation was avoided. CONCLUSIONS: Plastibell circumcision in the community is safe and effective. Detection of minor bleeding due to a slipped ring is important. Early management can avoid the risk of acquired phimosis due to cicatrix formation and can save parents of undue anxiety.


Subject(s)
Circumcision, Male/adverse effects , Phimosis/etiology , Circumcision, Male/instrumentation , Early Diagnosis , Hemorrhage/etiology , Humans , Male , Phimosis/prevention & control , Retrospective Studies
10.
Oncogene ; 30(33): 3585-98, 2011 Aug 18.
Article in English | MEDLINE | ID: mdl-21423218

ABSTRACT

A prominent feature of most cancers including Barrett's adenocarcinoma (BAC) is genetic instability, which is associated with development and progression of disease. In this study, we investigated the role of recombinase (hsRAD51), a key component of homologous recombination (HR)/repair, in evolving genomic changes and growth of BAC cells. We show that the expression of RAD51 is elevated in BAC cell lines and tissue specimens, relative to normal cells. HR activity is also elevated and significantly correlates with RAD51 expression in BAC cells. The suppression of RAD51 expression, by short hairpin RNA (shRNA) specifically targeting this gene, significantly prevented BAC cells from acquiring genomic changes to either copy number or heterozygosity (P<0.02) in several independent experiments employing single-nucleotide polymorphism arrays. The reduction in copy-number changes, following shRNA treatment, was confirmed by Comparative Genome Hybridization analyses of the same DNA samples. Moreover, the chromosomal distributions of mutations correlated strongly with frequencies and locations of Alu interspersed repetitive elements on individual chromosomes. We conclude that the hsRAD51 protein level is systematically elevated in BAC, contributes significantly to genomic evolution during serial propagation of these cells and correlates with disease progression. Alu sequences may serve as substrates for elevated HR during cell proliferation in vitro, as they have been reported to do during the evolution of species, and thus may provide additional targets for prevention or treatment of this disease.


Subject(s)
Adenocarcinoma/genetics , Alu Elements , Barrett Esophagus/genetics , Esophageal Neoplasms/genetics , Genome, Human , Rad51 Recombinase/physiology , Recombination, Genetic , Cell Line, Tumor , Humans , Loss of Heterozygosity , Mutation
11.
J Coll Physicians Surg Pak ; 20(2): 79-82, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20378031

ABSTRACT

OBJECTIVE: To determine the association between an abnormal ankle brachial index (ABI) and the presence of significant coronary artery disease (CAD) on coronary angiography. STUDY DESIGN: Cross-sectional, observational study. PLACE AND DURATION OF STUDY: The study was carried out at Sheikh Zayed Hospital, Lahore, from July to October 2007. METHODOLOGY: A series of 41 patients undergoing coronary angiography in Sheikh Zayed Hospital were selected and their ABI were calculated before the diagnostic coronary angiography. ABI calculations and coronary angiography reporting were done by separate individuals and data was analysed using SPSS 12.0. All patients undergoing diagnostic coronary angiography were included in the study except for those having peripheral arterial disease documented by lower extremity revascularization, lower extremity ulceration and lower extremity amputation. Proportion were compared using chi-square test with significance at p < 0.05. RESULTS: Out of the 41 patients 31 male (76%) and 10 female (24%), 3 patients (7.31%) had ABI < 0.9 and all 3 had triple vessel disease. Ten patients (24%) had ABI 0.91-0.99 and 2 (20%) of them had single vessel disease. Two (20%) had double vessel disease and 6 (60%) had triple vessel disease. Twenty four patients (58%) had ABI of 1.00-1.28 and 8 (33%) of these had single vessel disease, 3 (12%) had double vessel disease and 13 (55%) had triple vessel disease, while 4 patients had normal coronaries. A total of 22 patients were found to have triple vessel disease and only 3 (13.6%) of these 22 patients had an ABI < 0.9 which is statistically not significant (p=0.07). CONCLUSION: This study was not able to establish a direct association between ABI and significant CAD as only 3 patients out of 22 with triple vessel disease had an ABI < 0.9. However, an approximately log linear relationship was noted between ABI and CAD risk which means that not only the average CAD risk increased exponentially at values < 1.0 but also that the CAD risk continued to decline as ABI values increased above 1.0.


Subject(s)
Ankle Brachial Index , Coronary Artery Disease/diagnosis , Coronary Angiography , Coronary Artery Disease/physiopathology , Cross-Sectional Studies , Female , Humans , Male , Peripheral Arterial Disease/diagnosis , Peripheral Arterial Disease/physiopathology , Risk Assessment , Risk Factors , Severity of Illness Index
12.
Mol Cell Biol ; 29(10): 2546-55, 2009 May.
Article in English | MEDLINE | ID: mdl-19273600

ABSTRACT

The short form (S1b) of the prolactin receptor (PRLR) silences prolactin-induced activation of gene transcription by the PRLR long form (LF). The functional and structural contributions of two intramolecular disulfide (S-S) bonds within the extracellular subdomain 1 (D1) of S1b to its inhibitory function on the LF were investigated. Mutagenesis of the paired cysteines eliminated the inhibitory action of S1b. The expression of the mutated S1b (S1bx) on the cell surface was not affected, indicating native-like folding of the receptor. The constitutive JAK2 phosphorylation observed in S1b was not present in cells expressing S1bx, and JAK2 association was disrupted. BRET(50) (BRET(50) represents the relative affinity as acceptor/donor ratio required to reach half-maximal BRET [bioluminescence resonance energy transfer] values) showed decreased LF/S1bx heterodimeric-association and increased affinity in S1bx homodimerization, thus favoring LF homodimerization and prolactin-induced signaling. Computer modeling based on the PRLR crystal structure showed that minor changes in the tertiary structure of D1 upon S-S bond disruption propagated to the quaternary structure of the homodimer, affecting the dimerization interface. These changes explain the higher homodimerization affinity of S1bx and provide a structural basis for its lack of inhibitory function. The PRLR conformation as stabilized by S-S bonds is required for the inhibitory action of S1b on prolactin-induced LF-mediated function and JAK2 association.


Subject(s)
Disulfides/chemistry , Gene Expression Regulation , Protein Conformation , Protein Isoforms , Receptors, Prolactin , Animals , Cell Line , Cysteine/metabolism , Dimerization , Genes, Reporter , Humans , Janus Kinase 2/genetics , Janus Kinase 2/metabolism , Models, Molecular , Mutagenesis, Site-Directed , Mutation , Prolactin/metabolism , Protein Isoforms/chemistry , Protein Isoforms/genetics , Protein Isoforms/metabolism , Protein Multimerization , Receptors, Prolactin/chemistry , Receptors, Prolactin/genetics , Receptors, Prolactin/metabolism , Transcription, Genetic
13.
Osteoarthritis Cartilage ; 15(10): 1199-206, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17493841

ABSTRACT

OBJECTIVE: Cartilage loss as determined either by magnetic resonance imaging (MRI) or by joint space narrowing in X-rays is the result of cartilage erosion. However, metabolic processes within the cartilage that later result in cartilage loss may be a more accurate assessment method for early changes. Early biological processes of cartilage destruction are among other things, a combination of proteoglycan turnover, as a result of altered charge distributions, and local alterations in water content (edema). As water distribution is detectable by MRI, the aim of this study was to investigate cartilage homogeneity visualized by MRI related to water distribution, as a potential very early marker for early detection of knee osteoarthritis (OA). DESIGN: One hundred and fourteen right and left knees from 71 subjects aged 22-79 years were scanned using a Turbo 3D T(1) sequence on a 0.18T MRI Esaote scanner. The medial compartment of the tibial cartilage sheet was segmented using a fully automatic voxel classification scheme based on supervised learning. From the segmented cartilage sheet, homogeneity was quantified by measuring entropy from the distribution of signal intensities inside the compartment. For each knee an X-ray was acquired and the knees were categorized by the Kellgren and Lawrence (KL) index and the joint space width (JSW) was measured. The P-values for separating the groups by each of JSW, cartilage volume, cartilage mean intensity, and cartilage homogeneity were calculated using the unpaired t-test. RESULTS: The P-value for separating the group diagnosed as KL 0 from the group being KL 1 based on JSW, volume and mean signal intensity the values were P=0.9, P=0.4 and P=0.0009, respectively. In contrast, the P-value for homogeneity was P=0.0004. The precision of the measures assessed, as a test-retest root mean square coefficient of variation (RMS-CV%) was 3.9% for JSW, 7.4% for volume, 3.9% for mean signal intensity and 3.0% for homogeneity quantification. CONCLUSION: These data demonstrate that the distribution of components of the articular matrix precedes erosion, as measured by cartilage homogeneity related to water concentration. We show that homogeneity was able to separate early OA from healthy individuals in contrast to traditional volume and JSW quantifications. These data suggest that cartilage homogeneity quantification may be able to quantify early biochemical changes in articular cartilage prior to cartilage loss and thereby provide better identification of patients for OA trials who may respond better to medicinal intervention of some treatments. In addition, this study supports the feasibility of using low-field MRI in clinical studies.


Subject(s)
Cartilage, Articular/pathology , Knee Joint/pathology , Magnetic Resonance Imaging/methods , Osteoarthritis, Knee/pathology , Adult , Aged , Biomarkers , Cartilage, Articular/diagnostic imaging , Disease Progression , Early Diagnosis , Humans , Knee Joint/diagnostic imaging , Middle Aged , Multivariate Analysis , Osteoarthritis, Knee/diagnostic imaging , Radiography , Reproducibility of Results
14.
Aging Ment Health ; 10(4): 362-7, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16798628

ABSTRACT

Anxiety and agitation are common in people with dementia. Their consequences can be severe, including increased mortality rates and institutionalization. Despite the importance of these symptoms there is little literature in this area. Some studies have assumed that agitation is the outward manifestation of anxiety, while others have attempted to differentiate between them. The aim of this study was to investigate the relationship between anxiety and agitation in people with mild-to-moderate dementia. A secondary aim was to compare two measures of anxiety which have been used in people with dementia. A cross-sectional correlation design was used. Participants were 40 older adults with dementia. Agitation, anxiety, depression, and level of cognitive impairment were measured. The main finding from the study was that anxiety and agitation are associated in dementia. The degree of correlation did not support the use of agitation as a measure of anxiety. Anxiety symptoms of autonomic sensitivity were not correlated with agitation and could be used to differentiate between the two if this was required. The use of the Rating for Anxiety in Dementia (RAID) was supported as a measure of anxiety in people with dementia.


Subject(s)
Anxiety/psychology , Dementia/complications , Dementia/psychology , Psychomotor Agitation/psychology , Aged , Aged, 80 and over , Anxiety/etiology , Cognition , Cross-Sectional Studies , Depressive Disorder/complications , Depressive Disorder/psychology , Female , Humans , Male , Middle Aged , Psychiatric Status Rating Scales/statistics & numerical data , Psychomotor Agitation/etiology , Severity of Illness Index
15.
Mol Vis ; 10: 794-804, 2004 Oct 25.
Article in English | MEDLINE | ID: mdl-15529118

ABSTRACT

PURPOSE: Reorganization of cytoskeleton and membrane biogenesis are dynamically coordinated during lens fiber cell differentiation and development to produce an organ with precise dimensions and optical properties. Cargo vesicle trafficking is fundamental to cell elongation and has also been implicated in degenerative disease mechanisms. Alzheimer precursor protein (AbetaPP) acts with kinesin, synapsin, and synaptic vesicle proteins to mediate cargo vesicle transport and membrane fusion in neurons. In our previous studies we demonstrated that AbetaPP is also a key element in lens fiber cell formation, and in early-onset cataract that occurs along with early-onset Alzheimer disease in Down syndrome. In the present study we examine lens expression and regulation of a complement of genes associated with cargo and synaptic vesicle transport in neurons. METHODS: RT-PCR, immunoblot, and immunohistochemical methods were used to characterize expression of AbetaPP and kinesin associated motor proteins, synapsins, and synaptic vesicle proteins in mouse and rat embryonic, post-natal, and adult lenses. Phospho-specific anti-synapsin antibodies were used to determine the distributions of site-1 phosphorylated and dephosphorylated synapsin protein. RESULTS: We demonstrate that a substantial complement of cargo and synaptic vesicle proteins involved in AbetaPP mediated vesicle transport are expressed in lenses along the anterior-posterior axis of fiber cells in embryonic and adult lenses, consistent with vesicles, actin filaments, and neuron-like arrangement of microtubules in lenses shown by others. We identify temporal regulation of synapsins I, II, and III during embryonic and post-natal lens development consistent with their roles in neurons. Regulation of vesicle cytoskeleton attachment, actin polymerization, and the capacity to stimulate cell differentiation by synapsins are governed in large part by phosphorylation at a conserved Ser9 residue (site-1). We demonstrate discrete distributions of Ser9 phospho- and dephospho-synapsins along the axial length of rapidly elongating embryonic lens fiber cells, and decreased levels of site-1 phosphorylated synapsins in adult lenses. CONCLUSIONS: The present findings demonstrate several fundamental parallels between lens and neuron vesicle trafficking cell biology and development, and suggest that more extensive AbetaPP related vesicle trafficking disease mechanisms may be shared by lens and brain.


Subject(s)
Cell Differentiation , Gene Expression Regulation, Developmental/physiology , Lens, Crystalline/cytology , Lens, Crystalline/embryology , Nerve Tissue Proteins/genetics , Synapsins/genetics , Amyloid beta-Protein Precursor/metabolism , Animals , Brain/embryology , Brain/metabolism , Fluorescent Antibody Technique, Indirect , Immunoblotting , Kinesins/metabolism , Lens, Crystalline/metabolism , Male , Mice , Mice, Inbred C57BL , Nerve Tissue Proteins/metabolism , Phosphorylation , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction , Synapsins/metabolism , Synaptic Vesicles/metabolism
16.
Mol Vis ; 9: 179-83, 2003 May 01.
Article in English | MEDLINE | ID: mdl-12740567

ABSTRACT

PURPOSE: Beta- and gamma-secretases are proteases involved in the processing of the Alzheimer precursor protein (AbetaPP) that releases the transmembrane beta-amyloid fragment (Abeta), associated with age-dependent disease in lens and brain. Gamma-secretase is a protein complex containing Presenilin and Nicastrin proteins, which also processes Notch and other receptors involved in the eye and lens development. Neprilysin (NEP), a major protease involved in degrading Abeta, acts with beta- and gamma-secretases to regulate steady-state levels of Abeta. Previously, we demonstrated AbetaPP and Presenilin expression and processing in the lens and demonstrated cell degeneration in classic Alzheimer disease (AD) transgenic and systemic oxidative stress animal models, suggesting that additional AbetaPP processing proteins are also present in the lens. Here we investigate lens expression of beta-secretases, nicastrin and NEP proteins, and compare their protein distribution to Notch and Presenilin in lens. METHODS: RT-PCR was used to analyze mRNA transcripts. Immunoblots and immunohistochemistry were used to examine the protein expression and distribution of secretase and Abeta degrading proteins, as well as Presenilin and Notch proteins in mouse lenses. RESULTS: Beta-acting cleaving enzymes, BACE (BACE1) and BACE2, Nicastrin, Presenilins, Notch and NEP are expressed in the lens. In situ examination of protein distribution in lens indicates expression of each of these proteins is upregulated in peripheral elongating fiber cells at the lens equatorial margin and overlaps with Notch and Presenilin proteins, and also with the distribution of AbetaPP and Abeta proteins demonstrated in a previous study. Neprilysin exon 1-4 splicing, previously described as diagnostic for neuronal expression, also occurs in lens. CONCLUSIONS: BACE, BACE2, Nicastrin and NEP are expressed primarily in elongating peripheral fiber cells, overlapping with Notch, Presenilin, and AbetaPP protein distribution in lens, consistent with their role in regulating Notch and AbetaPP ectodomain shedding in lens. Lens expression of beta- and gamma-secretases together with NEP suggests these proteins may also regulate Abeta turnover in the lens. The presence of Abeta processing and degrading proteases in lens provides further evidence that Alzheimer-related cell biology is fundamentally involved in lens development, and provides additional evidence that mechanisms of Alzheimer pathophysiology can contribute to lens degeneration, suggesting further that therapeutics targeting Abeta proteases may be applicable to lens degenerative disease.


Subject(s)
Aspartic Acid Endopeptidases/metabolism , Lens, Crystalline/enzymology , Membrane Glycoproteins/metabolism , Membrane Proteins/metabolism , Neprilysin/metabolism , Receptors, Cell Surface , Transcription Factors , Amyloid Precursor Protein Secretases , Amyloid beta-Peptides/metabolism , Amyloid beta-Protein Precursor/metabolism , Animals , Aspartic Acid Endopeptidases/genetics , Blotting, Western , Endopeptidases , Fluorescent Antibody Technique, Indirect , Membrane Glycoproteins/genetics , Membrane Proteins/genetics , Mice , Mice, Inbred C57BL , Neprilysin/genetics , Presenilin-1 , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Receptor, Notch1 , Reverse Transcriptase Polymerase Chain Reaction , Up-Regulation
17.
Planta Med ; 67(8): 757-60, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11731923

ABSTRACT

Hypotensive effects of aloeemodin, aloin A, elgonica dimer A and bisbenzopyran from Aloe barbadensis have been studied. Aloeemodin has emerged as a potent hypotensive agent in current pharmacological investigations and caused 26 %, 52 %, and 79 % falls in mean arterial blood pressure at the corresponding doses of 0.5, 1, and 3 mg/kg in rats. The paper also describes the absolute configuration of elgonica dimer A (1).


Subject(s)
Aloe/chemistry , Anthraquinones/therapeutic use , Antihypertensive Agents/therapeutic use , Emodin/analogs & derivatives , Emodin/therapeutic use , Glucosides/therapeutic use , Hypertension/drug therapy , Phytotherapy , Plant Preparations/therapeutic use , Animals , Anthraquinones/chemistry , Anthraquinones/isolation & purification , Blood Pressure/drug effects , Dose-Response Relationship, Drug , Emodin/chemistry , Emodin/isolation & purification , Emodin/pharmacology , Glucosides/chemistry , Glucosides/isolation & purification , Magnetic Resonance Spectroscopy , Plant Leaves/chemistry , Plant Roots/chemistry , Rats
18.
Heart Surg Forum ; 3(1): 41-6, 2000.
Article in English | MEDLINE | ID: mdl-11064546

ABSTRACT

PURPOSE: Female gender has been shown to be an independent risk factor for mortality in coronary artery bypass graft (CABG) surgery. This report analyzes our early outcomes in 304 women who underwent off-pump coronary artery bypass (OPCAB) surgery at the Washington Hospital Center (Washington, DC) over the last 3 years to determine whether this is a safe approach for coronary bypass in women. METHODS: A retrospective review of 5528 cases of CABG bypass (on-pump) and 840 cases of OPCAB surgery, from June 1996 to July 1999, was performed. Women accounted for 1527 (27.6%) of the on-pump bypass cases and 304 (36.2%) of the OPCABs. All cases without cardiopulmonary bypass were included, with the majority of the most recent cases being multivessel revascularization. The data for analysis were obtained from our cardiac surgery database and included cases from all surgeons operating at the Washington Hospital Center, although the majority of off-pump cases were performed by only a few of these surgeons. RESULTS: The two groups were similar with respect to urgent cases, redos, and other comorbities including preoperative congestive heart failure, peripheral vascular disease, transient ischemic attack (TIA), cerebral vascular accident, and previous myocardial infarction. The mean age for the two groups was similar, 67 years for the off-pump group and 66 years for the on-pump group. The absolute number of all off-pump cases increased each year (from 175 to a total of 373), representing a corresponding increase in percentage of all coronary artery bypass procedures (from 9% to 16%). Of the total number of patients undergoing CABG, the percentage of women who underwent OPCAB doubled from 3% to 6% over the time period analyzed. The percentage of single-vessel cases in the off-pump group fell from 88% to 41% as multivessel bypasses became more routine However, the percentage of patients aged > 75 years was greater for the off-pump group (30%) than for the on-pump group (24%). Otherwise, the two groups differed only in diabetic disease (36% off-pump compared with 46% on-pump; p = 0.001) and previous transcatheter therapy (38% off-pump compared with 29% on-pump; p = 0.003). Patients who had OPCABs received fewer postoperative transfusions (40%) than the on-pump group (59%; p < 0.001). The off-pump group also had fewer neurological complications in the form of TIAs or strokes (0.3%) compared with the on-pump group (3.5%; p = 0.001). The mortality rate was 2.3% off -pump versus 4.1% on pump but did not reach statistical significance in this study (p =.12). CONCLUSION: Myocardial revascularization in women can be performed safely without cardiopulmonary bypass. In our series, the mortality for women receiving off-pump revascularization was lower than the on-pump cohorts despite an older age and higher incidence of diabetes. Although the absolute mortality rates did not reach statistical significance, we were encouraged that the mortality rate for women operated on without CPB dropped to the mortality rate typically seen in men. We also observed a favorable tendency in the off-pump group for a shorter length of stay and a lower incidences of transient ischemic attacks, strokes, post-op bleeding, and blood transfusions. A larger series of patients with multivariate analysis and/or a prospective trial will need to be analyzed in order to confirm our findings.


Subject(s)
Coronary Artery Bypass/methods , Aged , Aged, 80 and over , Coronary Artery Bypass/mortality , District of Columbia/epidemiology , Female , Humans , Length of Stay , Minimally Invasive Surgical Procedures/methods , Minimally Invasive Surgical Procedures/mortality , Postoperative Complications/epidemiology , Retrospective Studies , Survival Rate
19.
Planta Med ; 65(4): 331-4, 1999 May.
Article in English | MEDLINE | ID: mdl-10364838

ABSTRACT

Shamimin, a C-flavonol glucoside from Bombax ceiba leaves showed significant potency as a hypotensive agent at the doses of 15 mg/kg, 3 mg/kg, 1 mg/kg and significant hypoglycaemic activity at 500 mg/kg in Sprague-Dawley rats. Further studies revealed that it did not cause any mortality in mice at the dose of 1 g/kg but in rats 500 mg/kg is a lethal dose. Aqueous and methanolic extracts of Bombax ceiba leaves and one of its fractions were also subjected to pharmacological and toxicological screening.


Subject(s)
Antihypertensive Agents/pharmacology , Flavonoids/pharmacology , Glucose/analogs & derivatives , Hypoglycemic Agents/pharmacology , Plants/chemistry , Animals , Flavonoids/toxicity , Glucose/pharmacology , Glucose/toxicity , Mice , Rats , Rats, Sprague-Dawley
20.
Heart Surg Forum ; 2(1): 77-81, 1999.
Article in English | MEDLINE | ID: mdl-11276464

ABSTRACT

BACKGROUND: Coronary bypass surgery on the beating heart has been in existence since the inception of coronary revascularization. The advent and evolution of the heart-lung machine and cardioplegia have greatly advanced and expanded the realm of bypass surgery, allowing surgeons to perform precise coronary anastomoses in a still field of the arrested heart. The minimally invasive direct coronary artery bypass (MIDCAB) has been used primarily for grafting the left internal mammary artery (LIMA) to left anterior descending artery (LAD) and is gaining acceptance as a less invasive option. Dr. Frederico Benetti in Argentina championed the resurgence of beating heart surgery in 1985, and pioneered the left anterior thoracotomy MIDCAB procedure, which he has further refined to a xiphoid approach. The xiphoid incision is a simpler, less painful approach than that through a left anterior thoracotomy. METHODS: An incision is made through the xiphoid and, if necessary, into the tip of the sternum allowing the left side of the chest to be elevated. The distal LIMA is identified and dissected proximally to about the third interspace to give enough distance for a tensionless anastomosis. The pericardium is opened and the heart positioned to expose the LAD. Local stabilization for the LAD is obtained and the LIMA-to-LAD anastomosis is performed. RESULTS: The xiphoid MIDCAB approach was used for LIMA-to-LAD anastomosis in ten patients ranging in age from 52 to 86 years (mean age 73 years). Three patients underwent angioplasty of additionally obstructed vessels (so-called hybrid procedures) following initial MIDCAB. Despite high preoperative-risk profiles and Parsonnet scores, there were no deaths. However, two of the three hybrid patients had major complications resulting in a prolonged hospital stay. CONCLUSIONS: Initial clinical experience with xiphoid MIDCAB proves it is a feasible alternative to intercostal MIDCAB with the possible advantages of reduced pain and chest wall complications. Further investigation into this surgical approach is warranted.


Subject(s)
Coronary Artery Bypass , Internal Mammary-Coronary Artery Anastomosis , Minimally Invasive Surgical Procedures , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Treatment Outcome , Xiphoid Bone
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