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Biomedical subjects

S Zia

Publications and source records attributed to S Zia.

At least 19 recordsLinked to original sources
PubMed2004

Baseline disease knowledge assessment in patients with type 2 diabetes in a rural area of northwest of Pakistan.

OBJECTIVE: (1) To assess baseline disease related knowledge in patients with type 2 diabetes about their disease, its risk factors, signs/symptoms, related complications and suitable diet and (2) Is there an association between gender, duration of disease & age at diagnosis of diabetes and the above dependent variables. METHODS: A 20-item interview-based structured knowledge questionnaire was used to collect information. A total of 82, diabetic patients, mean age 55.2 (11.4 S.D.) years, ranging from 35-80 years, were interviewed. RESULTS: Statistically significant association was found between age at diagnosis and better understanding of risk factors, (OR = 1.20, P = 0.012 with 95% CI 0.85 - 0.98). Statistically significant association was found between gender and better understanding of word "diabetes" or "sugar" OR = 1.15, P = 0.051 with 95% Confidence interval 0.96-1.29). Statistically significant associations were found between gender and patients' better understanding of disease signs/symptoms (OR = 1.35, P = 0.005 with 95% CI 0.40-0.56). No significant associations were found between gender, duration of diabetes, age at diagnosis and patients' better understanding of disease related complications and suitable diet in diabetes. Duration of diabetes was not statistically associated with any of the dependent variables. CONCLUSION: Priority needs to be given by WHO education programmes for the development of diabetes education program in rural areas to give patients a better knowledge of their disease, to prevent premature morbidity and mortality associated with diabetes.

Adult↗
PubMed2004

Survival after myocardial infarction in patients with type 2 diabetes.

OBJECTIVES: To determine prospectively the survival of previously known diabetic patients admitted to coronary care unit with confirmed myocardial infarction (MI) over a one-year period and to assess the effects of gender, age, diabetes duration, hyperglycemia, hypertension, and anti-diabetic treatment on survival. METHODS: In this prospective cohort study, we followed 59 patients hospitalized with a confirmed myocardial infarction at 3 coronary care units, Peshawar (Pakistan), between May 1, 2000 and April 30, 2001. We analyzed survival using univariate and multivariate Cox Proportional hazards regression models to control for potentially confounding factors. RESULTS: A total of 17 (28.8%) subjects (7 male and 10 female) died. Survival was significantly associated with previous history of hypertension and duration of diabetes (HR = 3.40, 95% CI = 1.33-9.22, P = 0.001, and HR = 1.24, 95% CI = 1.05-1.45, P = 0.009, by Univariate Cox model, respectively). In multivariate analysis duration of diabetes was significantly associated with survival and Metformin treatment only, and Sulphonylurea & Metformin treatment together (P = 0.003, and 0.026, Multivariate Cox model, respectively). CONCLUSION: Our results suggested that diabetes is associated with markedly increased mortality in the presence of hypertension after acute myocardial infarction and support for aggressive treatment of coronary risk factors among diabetic patients.

Blood Glucose↗
PubMed2003

Health problems following Campylobacter jejuni enteritis in a Lancashire population.

OBJECTIVES: Campylobacter jejuni enteritis can lead to musculoskeletal, neuropathic or other health sequelae. We investigated the coexistence, seasonal occurrence, strain-type associations and impact on work capacity of different health problems following C. jejuni enteritis in a Lancashire population during 1999 and 2001. METHODS: A semistructured questionnaire was used to characterize health problems that occurred in the community after laboratory-confirmed episodes of C. jejuni enteritis. The questionnaire was posted to all adults in the Preston and Chorley area who developed C. jejuni enteritis in 1999 or 2001. All Campylobacter isolates from this population were serotyped. RESULTS: Several types of sequelae occurred consistently in both years, including the coexistence of musculoskeletal and neuropathic problems. There was no evidence of C. jejuni strain-type associations or seasonal preponderance for any type of sequela. The overall health impact of C. jejuni enteritis, as measured by workdays lost, was high in this population. CONCLUSIONS: A variety of health problems occur consistently following C. jejuni enteritis and substantially increase morbidity due to campylobacteriosis in the community.

Acute Disease↗
PubMed2003

Long-term management of bilateral metastases of renal cell carcinoma to the choroid plexus.

BACKGROUND: Metastatic tumors to the brain presenting exclusively in the choroid plexus are exceedingly rare. These events are frequently associated with renal cell carcinoma (RCC), of which all reported cases have been solitary lesions. METHODS: The authors present the unusual case of a patient with metastatic RCC who developed bilateral tumors of the choroid plexus. These tumors, one of which was confirmed to be metastatic RCC by histologic analysis, were treated over a 5-year period with a combination of interventions, including surgical resection, stereotactic radiosurgery, and chemotherapy, in conjunction with continual radiological monitoring. FINDINGS: Follow-up over a 5-year period demonstrated good control of the patient's intracranial disease and very little neurologic sequelae. INTERPRETATION: This strategy was successful in keeping the patient in good health with minimal neurological symptoms, despite the bilateral nature of the disease and its generally poor prognosis.

Carcinoma, Renal Cell↗
PubMed2001

Programmed cell death of keratinocytes culminates in apoptotic secretion of a humectant upon secretagogue action of acetylcholine.

The programmed cell death of the stratified squamous epithelial cells comprising human epidermis culminates in abrupt transition of viable granular keratinocytes (KC) into dead corneocytes sloughed by the skin. The granular cell-corneocyte transition is associated with a loss in volume and dry cell weight but the mechanism for and biological significance of this form of keratinocyte apoptosis remain obscure. We show that terminally differentiated KC extrude into the intercellular spaces of living epidermis the cytoplasmic buds containing randomly congregated components of the cytosol as well as filaggrin, a precursor of the natural moisturizing factor. The discharge of secretory product is reminiscent of holocrine secretion, suggesting the term 'apoptotic secretion' for this novel, essential step in the process of cornification. The secretory product may become a part of the glycocalyx (a.k.a. 'intercellular cement substance' of epidermis) and serve as a humectant that counterbalances the osmotic pressure imposed by the natural moisturizing factor located in the stratum corneum comprised by corneocytes. The apoptotic secretion commences upon secretagouge action of acetylcholine which is synthesized and released by KC. A combination of a cholinergic nicotinic agonist and a muscarinic antagonist which increases intracellular calcium levels is required to trigger the apoptotic secretion. Analysis of the relative amounts of cholinergic enzymes and receptors expressed by KC capable of secretion and the pharmacological profiles of secretion regulation revealed an upward concentration gradient of free acetylcholine in epidermis which may provide for its unopposed secretagogue action via the m1 muscarinic and the alpha7, and alpha9 nicotinic receptor types expressed by KC at the latest stage of their development in the epidermis.

Acetylcholine↗
PubMed2000

Selenium altered the levels of lipids, lipid peroxidation, and sulfhydryl groups in straitum and thalamus of rat.

The effect of sodium selenite (0.05, 0.1, and 0.2 mg/kg body weight, i.p.) on the lipid levels (total lipids, phospholipids, cholesterol, gangliosides), thiobarbituric acid reactive substance (TBARS), and sulfhydryl group (-SH) in the striatum and thalamus of a male Wistar rat was studied after 7 d of treatment. The level of total lipids and cholesterol was significantly and dose-dependently elevated in the striatum and thalamus with 0.1 and 0.2 mg/kg of sodium selenite. However, the cholesterol level was significantly increased only with 0.2 mg/kg of sodium selenite in the thalamus. The level of phospholipids and gangliosides was more significant with 0.1 mg/kg of sodium selenite as compared to 0.2 mg. No significant alteration on the gangliosides level was observed in the thalamus with various doses of sodium selenite although the elevation with 0.2 mg dose was 25.9%. The content of TBARS was elevated dose dependently in striatum, but its level was depleted significantly with 0.1-mg/kg dose of sodium selenite in the thalamus. The level of the -SH group was significantly depleted in the striatum with 0.1-mg/kg dose of sodium selenite; conversely, this dose has significantly elevated the levels of -SH group in the thalamus.

Animals↗
PubMed2000

Joint position sense is impaired by Parkinson's disease.

The abilities of Parkinson's disease (PD) patients, taking routine medication, and of control subjects, to discriminate bilateral differences in the static angular positions of the two elbow joints were studied during passive (subject relaxed) and active (subject contracting to hold position) conditions. On each trial, one of the subject's elbows served as the reference joint (angle 60 degrees) and the other as the test joint (angular range, 54 degrees to 69 degrees, at 3 degree intervals). Subjects, with eyes closed, were required to discriminate the relative angles of the two elbows. In Experiments 1 (passive condition) and 2 (active condition), parkinsonians (n = 12) gave significantly fewer correct responses, pooled across sides, than did controls (n = 12), both in total scores across all angles and at individual test angles of 57 degrees and 63 degrees. In Experiment 3 (passive condition), derivation of conventional psychophysical variables indicated that both the difference limen (DL; threshold) and Weber ratio (WR; discriminatory sensitivity, independent of absolute stimulus values; same as DL/PSE) values of patients (n = 6) were significantly larger than those of controls (n = 6), in the absence of a significant difference between groups in the point of subjective equality (PSE). Our results provide clear evidence of a quantitative impairment of joint position sense in PD patients.

Adult↗
PubMed2000

Receptor-mediated inhibition of keratinocyte migration by nicotine involves modulations of calcium influx and intracellular concentration.

Early stages of wound healing rely on the ability of keratinocytes (KCs) to move over the denuded dermis to re-epithelialize the defect. The agarose gel keratinocyte outgrowth system (AGKOS) is an in vitro model of skin re-epithelialization designed to study the migratory function of KCs. Endogenously secreted acetylcholine controls crawling locomotion of KCs in AGKOS by binding to the cholinergic receptors of both the nicotinic and the muscarinic classes that are expressed by KCs. In this study, we used AGKOS to elucidate the nicotinic pathway of cholinergic control of keratinocyte migration. Activation of the nicotinic acetylcholine receptors decreased the migration distance of KC in a dose-dependent fashion without altering cell viability. Nicotine also increased in a dose-dependent manner transmembrane influx of (45)Ca(2+), and caused a transient rise in the concentration of [Ca(2+)](i). Perfect correlation between concentration responses found in the migration and (45)Ca(2+) influx assays suggested that nicotine-induced inhibition of crawling locomotion relies on modulation of Ca(2+) metabolism in KCs. The effects of nicotine could be mediated by the alpha3- and the alpha7-containing nicotinic receptors visualized on KCs by immunostaining. Long-term incubation with nicotine up-regulated alpha7 and down-regulated alpha3 expression. Thus, nicotine exerts inhibitory effects on keratinocyte migration, and Ca(2+) serves as a second messenger in the signaling pathway. These results help explain deleterious effects of nicotine on wound re-epithelialization, and suggest that smoking may delay wound healing via nicotinic receptor-mediated pathway.

Animals↗
PubMed1999

Human skin fibroblasts express m2, m4, and m5 subtypes of muscarinic acetylcholine receptors.

Previous studies have demonstrated that muscarinic acetylcholine receptors (mAChRs) are expressed by human skin fibroblasts (HSF). We have identified the molecular subtypes of these receptors by reverse transcription-polymerase chain reaction (RT-PCR), using m1-m5 subtype-specific primers. These experiments showed that only mRNAs for m2, m4, and m5 mAChR subtypes are present in HSF. The RT-PCR products were characterized by restriction analysis and Southern blotting. Northern blot analysis showed the presence of m2 and m4 mAChR RNA. Rabbit antibodies were raised using a synthetic peptide as immunogen corresponding to the C-terminus of the m2 protein and were used to visualize fibroblast mAChRs. Cell membranes of HSF in cell culture and specimens of normal human skin had a unique staining pattern specific for anti-m2 antibody, as well as for antibodies against m4 and m5. In Western blots of fibroblast proteins, the antibodies visualized the m2 receptor at 65 kDa, m4 at 70 kDa, and m5 at 95 kDa. The function of fibroblast mAChRs was examined by measuring muscarinic effects on intracellular free Ca2+ concentration ([Ca2+]i). Muscarine increased transiently [Ca2+]i in cultured HSF. This effect could be abolished by the muscarinic antagonist atropine. Thus, the results of this study showed that HSF express m2, m4, and m5 mAChR subtypes, and that fibroblast mAChRs are coupled to the regulation of [Ca2+]i.

Adult↗
PubMed1999

Cloning and expression of the Na+/H+ exchanger from Amphiuma RBCs: resemblance to mammalian NHE1.

The cDNA encoding the Na+/H+ exchanger (NHE) from Amphiuma erythrocytes was cloned, sequenced, and found to be highly homologous to the human NHE1 isoform (hNHE1), with 79% identity and 89% similarity at the amino acid level. Sequence comparisons with other NHEs indicate that the Amphiuma tridactylum NHE isoform 1 (atNHE1) is likely to be a phylogenetic progenitor of mammalian NHE1. The atNHE1 protein, when stably transfected into the NHE-deficient AP-1 cell line (37), demonstrates robust Na+-dependent proton transport that is sensitive to amiloride but not to the potent NHE1 inhibitor HOE-694. Interestingly, chimeric NHE proteins constructed by exchanging the amino and carboxy termini between atNHE1 and hNHE1 exhibited drug sensitivities similar to atNHE1. Based on kinetic, sequence, and functional similarities between atNHE1 and mammalian NHE1, we propose that the Amphiuma exchanger should prove to be a valuable model for studying the control of pH and volume regulation of mammalian NHE1. However, low sensitivity of atNHE1 to the NHE inhibitor HOE-694 in both native Amphiuma red blood cells (RBCs) and in transfected mammalian cells distinguishes this transporter from its mammalian homologue.

Amino Acid Sequence↗
PubMed1998

Identification and mapping of keratinocyte muscarinic acetylcholine receptor subtypes in human epidermis.

Acetylcholine mediates cell-to-cell communications in the skin. Human epidermal keratinocytes respond to acetylcholine via two classes of cell-surface receptors, the nicotinic and the muscarinic cholinergic receptors. High affinity muscarinic acetylcholine receptors (mAChR) have been found on keratinocyte cell surfaces at high density. These receptors mediate effects of muscarinic drugs on keratinocyte viability, proliferation, adhesion, lateral migration, and differentiation. In this study, we investigated the molecular structure of keratinocyte mAChR and their location in human epidermis. Polymerase chain reaction amplification of cDNA sequences uniquely present within the third cytoplasmic loop of each subtype demonstrated the expression of the m1, m3, m4, and m5 mAChR subtypes. To visualize these mAChR, we raised rabbit anti-sera to synthetic peptide analogs of the carboxyl terminal regions of each subtype. The antibodies selectively bound to keratinocyte mAChR subtypes in immunoblotting membranes and epidermis, both of which could be abolished by preincubating the anti-serum with the peptide used for immunization. The immunofluorescent staining patterns produced by each antibody in the epidermis suggested that the profile of keratinocyte mAChR changes during epidermal turnover. The semiquantitative analysis of fluorescence revealed that basal cells predominantly expressed m3, prickle cells had equally high levels of m4 and m5, and granular cells mostly possessed m1. Thus, the results of this study demonstrate for the first time the presence of m1, m3, m4, and m5 mAChR in epidermal keratinocytes. Because keratinocytes express a unique combination of mAChR subtypes at each stage of their development in the epidermis, each receptor may regulate a specific cell function. Hence, a single cytotransmitter, acetylcholine, and muscarinic drugs may exert different biologic effects on keratinocytes at different stages of their maturation.

Antibody Specificity↗
PubMed1997

Nicotine enhances expression of the alpha 3, alpha 4, alpha 5, and alpha 7 nicotinic receptors modulating calcium metabolism and regulating adhesion and motility of respiratory epithelial cells.

The purpose of this study was to investigate the possibility of direct toxic effects of nicotine (Nic) on human bronchial epithelial cells (BEC) suggested by our previous findings of functional nicotinic acetylcholine receptors (nAChRs) in the epithelial cells lining mucocutaneous membranes. We now demonstrate for the first time that human and murine BEC both in vivo and in vitro express functional nAChRs, and that classic alpha 3, alpha 4, alpha 5 and alpha 7 subunits can contribute to formation of these acetylcholine-gated ion channels. In human bronchial and mouse lung tissues, and in cultures of human BEC, the nAChRs were visualized by subunit-specific antibodies on the cell membranes, particularly at the sites of cell-to-cell contacts. The epithelial cells of submucosal glands abundantly expressed alpha 7 nAChRs. Smoking significantly (p < 0.05) increased the relative numbers of nAChRs, and this effects could be reproduced in cultures of BEC exposed to 10 microM Nic. At a higher dose, Nic decreased the relative numbers of alpha 5-containing nAChRs, suggesting a role for receptor desensitization. The function of the nAChR channels expressed by BEC was demonstrated by biphasic increase in the concentrations of intracellular calcium ([Ca++]i) in response to activation of the channel by Nic and fluctuations of [Ca++]i due to channel blockade by mecamylamine (Mec). Long-term exposure to milimolar concentrations of Nic resulted in a steady increase of [Ca++]i, which may lead to cell damage. The biological roles of epithelial nAChRs apparently involve regulation of cell-to-cell communications, adhesion and motility, because Mec caused rapid and profound changes in these cell functions which were reversible by Nic. An over exposure of BEC to Nic, however, produced an antagonist-like effect, suggesting that the pathobiological effects of Nic toxicity might result from both activation of nAChR channels and nAChR desensitization. We conclude that medical consequences of smoking can be mediated by direct toxic effects of inhaled Nic on the respiratory tissues wherein Nic specifically binds to and activates the nicotinic ion channels present on the cell surfaces of BEC. We believe that outside the neural system Nic interferes with functioning of non-neuronal cholinergic networks by displacing from nAChR its natural ligand acetylcholine which acts as a local hormone or cytokine in a variety of non-neuronal locations.

Adolescent↗
PubMed1994

Acetaldehyde-induced stimulation of collagen synthesis and gene expression is dependent on conditions of cell culture: studies with rat lipocytes and fibroblasts.

Acetaldehyde has been proposed as a mediator of fibrogenesis in alcoholic liver disease, based in part on its ability to stimulate collagen synthesis by hepatic lipocytes in late primary or passaged culture. In this study, we examined the effect of acetaldehyde on rat lipocytes and fibroblasts at various stages of culture, in an effort to determine whether culture-related events influence responsiveness to this compound. Lipocytes from normal rat liver were studied in primary culture at 3 and 7 days after plating; fibroblasts were studied in subculture, at subconfluent and confluent densities. Both cell types were incubated with 100 microM acetaldehyde for 24 hr followed by measurement of collagen synthesis and type I collagen gene expression. Acetaldehyde had no effect on lipocytes at either 3 or 7 days in primary culture. The inability of acetaldehyde to stimulate collagen synthesis in primary culture was not attributable to toxicity, because cell morphology and total protein synthesis were identical in both treated and untreated cultures. Fibroblasts exhibited a variable response to acetaldehyde that was dependent on cell density: subconfluent cells contained similar amounts of type I collagen mRNA in both the presence and absence of acetaldehyde, whereas confluent cells exhibited a 2- to 3-fold increase in collagen mRNA levels upon acetaldehyde exposure. To determine whether quiescent lipocytes would respond to acetaldehyde in a culture system that mimics the hepatic environment in vivo, lipocytes were plated in coculture with hepatocytes on a basement membrane gel and incubated with 20 mM ethanol for 72 hr. Direct communication between these two cell types did not provoke lipocyte activation, even in the setting of ethanol oxidation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗
PubMed1992

Effects of an interferon inducer bropirimine on bleomycin-induced lung fibrosis in hamsters.

The antifibrotic effect of an interferon inducer, bropirimine (2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone, ABPP) was evaluated in bleomycin (BLM)-hamster model of lung fibrosis. ABPP is an orally active biological response modifier and has immunomodulatory, antiviral, and antineoplastic activities. The hamsters were randomized in four groups and treated with either bropirimine (100 mg/kg, intraperitoneally) suspended in carboxymethylcellulose (CMC, 10 mg/10 mg/ml) or CMC alone each day for sixteen days. After two days, the hamsters received either single bolus of BLM (7.5 U/5 ml/kg) or an equivalent volume of saline by the transoral endotracheal route. Groupings were assigned as: CMC + saline (CS), ABPP + saline (AS), CMC + BLM (CB) and ABPP + BLM (AB). Animals were sacrificed at fourteen days after intratracheal installation of either BLM or saline. Their lungs were lavaged and processed for morphometric and biochemical studies. ABPP had little effect in preventing BLM-induced weight loss and lung injury. ABPP was found to reduce the BLM-induced accumulation of collagen in the lung as measured by hydroxyproline content. The hamsters in AB group had significantly less collagen than the hamsters in CB group: 995 and 1157 micrograms hydroxyproline/lung, respectively. Administration of ABPP prevented the BLM-induced increase in the lung prolyl hydroxylase activity. The total number of monocytes and eosinophils recovered from the bronchoalveolar lavage fluid (BALF) of the AB group were significantly lower than that of the animals in CB group. However, the BALF supernatant protein content from animals in AB group (7.9 mg/lung) was significantly higher than that of CB group (4.5 mg/lung).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Development of a bleomycin hamster model of subchronic lung fibrosis.

The existing bleomycin (BLM)-rodent model of lung fibrosis requires large doses and is often associated with morbidity and high mortality. We have developed an intratracheal multiple-dose BLM-hamster model of lung fibrosis. In this model, 3 consecutive doses of BLM (2.5 U, 2.0 U and 1.5 U/5mL/kg) were instilled intratracheally, one dose per week. The hamsters were killed at 10, 20, 30, 60 and 90 days after the last IT instillation and the lungs were lavaged or perfused with saline. This regimen of BLM administration was devoid of morbidity and caused only 6% overall mortality. Lung prolyl hydroxylase activity at 10 days and hydroxyproline content at 20, 30, 60 and 90 days were significantly higher than noted for the controls. Bronchoalveolar lavage fluid-supernatant protein and the total number of recovered cells of all types were significantly higher than observed for the controls at all times, except at 90 days. Lungs showed a multifocal mixed mononuclear infiltrate at 10 and 20 days and septal fibrosis, which was most severe and organized at 30 days and less severe at 60 and 90 days. The parenchymal lesions were significantly greater than those of the controls at all times, except at 10 days. This model, which required only 6 U BLM/kg, induced a moderate level of lung fibrosis. It has been concluded, therefore, that this model, inasmuch as it is not associated with an overwhelmingly acute inflammation, would be more applicable for screening potential antifibrotic agents than existing models of lung fibrosis.

Animals↗
PubMed1991

Plateletpheresis with the new Fresenius AS 104 blood cell separator.

Among the many blood cell separators introduced into the international market in these last few years, the Fresenius AS 104 represents an advanced and safe thrombocytapheresis machine whose development took advantage of extensive worldwide experience with blood cell separation. Nonetheless the AS 104 has generated most interest in West Germany and most, if not all, the studies published on its platelet collection efficiency have been carried out in that country. It is normally reported that from 2.7 to 3.5 x 10(11) platelets can be collected in approximately 80 minutes. Since these results could not be duplicated routinely in our hemapheresis unit, we set up a study by modifying the standard procedure. It was possible to reduce the procedure time and to collect platelet concentrates containing more than 4 x 10(11) cells on a routine basis by using the following procedure: ACD-A/blood ratio 1:10; Interface position 6:2; blood flow rate always exceeding 65 mL/min; rpm 1750; cell collection from 4 to 7 mL/min; volume of blood processed 3.6 L followed by the rinsing of the system with 200 ml of saline; extraction of the content of the secondary separation chamber by the action of the plasma pump working at 20 mL/min for 2 min. With this procedure the platelet yield in 34 collections exceeded 3.1 x 10(11) and averaged 4.06 x 10(11). The procedure time was reduced to 56.5 minutes with a mean blood flow rate of 62.3 mL/min. The leukocyte and erythrocyte contamination of the products were in the range of 1 x 10(7) and 1 x 10(8) respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation Studies as Topic↗